Karen Taraszka Hastings

Interests

Research

Autoimmune and inflammatory disease; Bone, skin and mucosal disease; Cancer; Host-microbe interactions and immunology

Courses

Scholarly Contributions

Chapters

• Hastings, K. T. (2019). Innate and adaptive immune responses to cancer. In Fundamentals of Cancer Prevention. New York, NY: Springer-Verlag.
• Meador, L. R., & Hastings, K. T. (2017). Gamma-interferon-inducible lysosomal thiol reductae. In Encylopedia of Signaling Molecules. New York, NY: Springer-Verlag.
• Rausch, M. P., & Hastings, K. T. (2017). Immune checkpoint inhibitors in the treatment of melanoma: for basic science to clinical application. In Cutaneous Melanoma: Etiology and Therapy(pp 121-142). Brisbane, Australia: Codon Publications.
• Hastings, K. T. (2014). Innate and adaptive immune responses to cancer. In Fundamentals of Cancer Prevention(pp 81-122). New York, NY: Springer-Verlag.
• Hastings, K. T., Glusac, E. J., Wilson, L. D., & Girardi, M. (2010). Mycosis fungoides and Sezary syndrome: pathophysiology and pathology. In Lymphoid Neoplasms. London England.
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  Hodder ArnoldMagrath, I, ed.; 3rd edition
• Hastings, K. T. (2008). Innate and adaptive immune responses to cancer. In Fundamentals of Cancer Prevention. New York, NY: Springer-Verlag.
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  Alberts, DS, Hess, LM, eds.; 2nd edition
• Hastings, K. T. (2005). Erythema multiforme, Stevens-Johnson syndrome, and toxic epidermal necrolysis. In Field Guide to Internal Medicine. Philadelphia, PA: Lippincott Williams and Wilkins.
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  Smith, D, Sullivan, L, Hay, S, eds.
• Hastings, K. T., & Dover, J. S. (2004). Erythema multiforme, Stevens-Johnson syndrome, and toxic epidermal necrolysis. In Conn's Current Therapy(pp 893-895). Philadelphia, PA.
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  Rakel, RE, Bope, ET, eds
• Hastings, K. T., & Girardi, M. (2003). Treatment of cutanoue T cell lymphoma: advances in understanding disease behavior and implications for management. In Year Book of Dermatology and Dermatologic Surgery(pp 1-26). Mosby, St. Louis.

Journals/Publications

• Adams, A. C., Macy, A. M., Kang, P., Castro-Ochoa, K. F., Wijeratne, E. M., Xu, Y. M., Liu, M. X., Charos, A., Bosenberg, M. W., Gunatilaka, A. A., Sertil, A. R., & Hastings, K. T. (2022). Physachenolide C induces complete regression of established murine melanoma tumors via apoptosis and cell cycle arrest. Translational oncology, 15(1), 101259.
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  Melanoma is an aggressive skin cancer that metastasizes to other organs. While immune checkpoint blockade with anti-PD-1 has transformed the treatment of advanced melanoma, many melanoma patients fail to respond to anti-PD-1 therapy or develop acquired resistance. Thus, effective treatment of melanoma still represents an unmet clinical need. Our prior studies support the anti-cancer activity of the 17β-hydroxywithanolide class of natural products, including physachenolide C (PCC). As single agents, PCC and its semi-synthetic analog demonstrated direct cytotoxicity in a panel of murine melanoma cell lines, which share common driver mutations with human melanoma; the IC values ranged from 0.19-1.8 µM. PCC treatment induced apoptosis of tumor cells both in vitro and in vivo. In vivo treatment with PCC alone caused the complete regression of established melanoma tumors in all mice, with a durable response in 33% of mice after discontinuation of treatment. T cell-mediated immunity did not contribute to the therapeutic efficacy of PCC or prevent tumor recurrence in YUMM2.1 melanoma model. In addition to apoptosis, PCC treatment induced G0-G1 cell cycle arrest of melanoma cells, which upon removal of PCC, re-entered the cell cycle. PCC-induced cycle cell arrest likely contributed to the in vivo tumor recurrence in a portion of mice after discontinuation of treatment. Thus, 17β-hydroxywithanolides have the potential to improve the therapeutic outcome for patients with advanced melanoma.
• Adams, A., Borden, E. S., Macy, A. M., Thomson, N., Cui, H., Gimbel, M., Wilson, M. A., Buetow, K. H., Roe, D. J., DiCaudo, D., Homsi, J., & Hastings, K. T. (2022). High GILT expression is associated with improved survival in metastatic melanoma patients treated with immune checkpoint inhibition. Cancers.
• Borden, E. S., Ghafoor, S., Buetow, K. H., LaFleur, B., Wilson, M. A., & Hastings, K. T. (2022). NeoScore integrates characteristics of the neoantigen:MHC class I interaction and expression to accurately prioritize immunogenic neoantigens. Journal of Immunology.
• Hastings, K. T., Buetow, K. H., Wilson, M. A., & Borden, E. S. (2022). Cancer neoantigens: challenges and future directions for prediction, prioritization and validation. Frontiers in Oncology.
• Borden, E. S., Adams, A. C., Buetow, K. H., Wilson, M. A., Bauman, J. E., Curiel-Lewandrowski, C., Chow, H. S., LaFleur, B. J., & Hastings, K. T. (2021). Shared Gene Expression and Immune Pathway Changes Associated with Progression from Nevi to Melanoma. Cancers, 14(1).
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  There is a need to identify molecular biomarkers of melanoma progression to assist the development of chemoprevention strategies to lower melanoma incidence. Using datasets containing gene expression for dysplastic nevi and melanoma or melanoma arising in a nevus, we performed differential gene expression analysis and regularized regression models to identify genes and pathways that were associated with progression from nevi to melanoma. A small number of genes distinguished nevi from melanoma. Differential expression of seven genes was identified between nevi and melanoma in three independent datasets. C1QB, CXCL9, CXCL10, DFNA5 (GSDME), FCGR1B, and PRAME were increased in melanoma, and SCGB1D2 was decreased in melanoma, compared to dysplastic nevi or nevi that progressed to melanoma. Further supporting an association with melanomagenesis, these genes demonstrated a linear change in expression from benign nevi to dysplastic nevi to radial growth phase melanoma to vertical growth phase melanoma. The genes associated with melanoma progression showed significant enrichment of multiple pathways related to the immune system. This study demonstrates (1) a novel application of bioinformatic approaches to aid clinical trials of melanoma chemoprevention and (2) the feasibility of determining a gene signature biomarker of melanomagenesis.
• Macy, A. M., Adams, A. C., Saboda, K., Dickinson, S. E., Glembocki, D. J., Roe, D. J., & Hastings, K. T. (2021). Solar simulated light induces cutaneous squamous cell carcinoma in inbred mice: a clinically relevant model to investigate T cell responses. Journal of Investigative Dermatology, 141(12), 2990-2993. doi:https://doi.org/10.1016/j.jid.2021.06.005
• Rausch, M. P., Meador, L. R., Metzger, T. C., Li, H., Qiu, S., Anderson, M. S., & Hastings, K. T. (2020). GILT in Thymic Epithelial Cells Facilitates Central CD4 T Cell Tolerance to a Tissue-Restricted, Melanoma-Associated Self-Antigen. Journal of immunology (Baltimore, Md. : 1950), 204(11), 2877-2886.
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  Central tolerance prevents autoimmunity, but also limits T cell responses to potentially immunodominant tumor epitopes with limited expression in healthy tissues. In peripheral APCs, γ-IFN-inducible lysosomal thiol reductase (GILT) is critical for MHC class II-restricted presentation of disulfide bond-containing proteins, including the self-antigen and melanoma Ag tyrosinase-related protein 1 (TRP1). The role of GILT in thymic Ag processing and generation of central tolerance has not been investigated. We found that GILT enhanced the negative selection of TRP1-specific thymocytes in mice. GILT expression was enriched in thymic APCs capable of mediating deletion, namely medullary thymic epithelial cells (mTECs) and dendritic cells, whereas TRP1 expression was restricted solely to mTECs. GILT facilitated MHC class II-restricted presentation of endogenous TRP1 by pooled thymic APCs. Using bone marrow chimeras, GILT expression in thymic epithelial cells (TECs), but not hematopoietic cells, was sufficient for complete deletion of TRP1-specific thymocytes. An increased frequency of TRP1-specific regulatory T (Treg) cells was present in chimeras with increased deletion of TRP1-specific thymocytes. Only chimeras that lacked GILT in both TECs and hematopoietic cells had a high conventional T/Treg cell ratio and were protected from melanoma challenge. Thus, GILT expression in thymic APCs, and mTECs in particular, preferentially facilitates MHC class II-restricted presentation, negative selection, and increased Treg cells, resulting in a diminished antitumor response to a tissue-restricted, melanoma-associated self-antigen.
• Rausch, M. P., Meador, L. R., Metzger, T. C., Li, H., Qiu, S., Anderson, M. S., & Hastings, K. T. (2020). GILT in thymic epithelial cells facilitates central CD4 T cell tolerance to a tissue-restricted, melanoma-associated self antigen. Journal of Immunology.
• Borden, E. S., Kang, P., Natri, H. M., Phung, T. N., Wilson, M. A., Buetow, K. H., & Hastings, K. T. (2019). Neoantigen Fitness Model Predicts Lower Immune Recognition of Cutaneous Squamous Cell Carcinomas Than Actinic Keratoses. Frontiers in immunology, 10, 2799.
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  A low percentage of actinic keratoses progress to develop into cutaneous squamous cell carcinoma. The immune mechanisms that successfully control or eliminate the majority of actinic keratoses and the mechanisms of immune escape by invasive squamous cell carcinoma are not well-understood. Here, we took a systematic approach to evaluate the neoantigens present in actinic keratosis and cutaneous squamous cell carcinoma specimens. We compared the number of mutations, the number of neoantigens predicted to bind MHC class I, and the number of neoantigens that are predicted to bind MHC class I and be recognized by a T cell receptor in actinic keratoses and cutaneous squamous cell carcinomas. We also considered the relative binding strengths to both MHC class I and the T cell receptor in a fitness cost model that allows for a comparison of the immune recognition potential of the neoantigens in actinic keratosis and cutaneous squamous cell carcinoma samples. The fitness cost was subsequently adjusted by the expression rates of the neoantigens to examine the role of neoantigen expression in tumor immune evasion. Our analyses indicate that, while the number of mutations and neoantigens are not significantly different between actinic keratoses and cutaneous squamous cell carcinomas, the predicted immune recognition of the neoantigen with the highest expression-adjusted fitness cost is lower for cutaneous squamous cell carcinomas compared with actinic keratoses. These findings suggest a role for the down-regulation of expression of highly immunogenic neoantigens in the immune escape of cutaneous squamous cell carcinomas. Furthermore, these findings highlight the importance of incorporating additional factors, such as the quality and expression of the neoantigens, rather than focusing solely on tumor mutational burden, in assessing immune recognition potential.
• Buetow, K. H., Meador, L. R., Menon, H., Lu, Y. K., Brill, J., Cui, H., Roe, D. J., DiCaudo, D. J., & Hastings, K. T. (2019). High GILT Expression and an Active and Intact MHC Class II Antigen Presentation Pathway Are Associated with Improved Survival in Melanoma. Journal of immunology (Baltimore, Md. : 1950), 203(10), 2577-2587.
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  The MHC class I Ag presentation pathway in melanoma cells has a well-established role in immune-mediated destruction of tumors. However, the clinical significance of the MHC class II Ag presentation pathway in melanoma cells is less clear. In Ag-presenting cells, IFN-γ-inducible lysosomal thiol reductase (GILT) is critical for MHC class II-restricted presentation of multiple melanoma Ags. Although not expressed in benign melanocytes of nevi, GILT and MHC class II expression is induced in malignant melanocytes in a portion of melanoma specimens. Analysis of The Cancer Genome Atlas cutaneous melanoma data set showed that high GILT mRNA expression was associated with improved overall survival. Expression of IFN-γ, TNF-α, and IL-1β was positively associated with GILT expression in melanoma specimens. These cytokines were capable of inducing GILT expression in human melanoma cells in vitro. GILT protein expression in melanocytes was induced in halo nevi, which are nevi undergoing immune-mediated regression, and is consistent with the association of GILT expression with improved survival in melanoma. To explore potential mechanisms of GILT's association with patient outcome, we investigated pathways related to GILT function and expression. In contrast to healthy skin specimens, in which the MHC class II pathway was nearly uniformly expressed and intact, there was substantial variation in the MHC class II pathway in the The Cancer Genome Atlas melanoma specimens. Both an active and intact MHC class II pathway were associated with improved overall survival in melanoma. These studies support a role for GILT and the MHC class II Ag presentation pathway in melanoma outcome.
• Hastings, K. T., Elizalde, D., Muppana, L., Levine, S., Kamel, C. M., Ingram, W. M., Kirkpatrick, J. T., Hu, C., Rausch, M. P., & Gallitano, A. L. (2017). Nab2 maintains thymus cellularity with aging and stress. Molecular immunology, 85, 185-195.
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  Thymic cellularity is influenced by a variety of biological and environmental factors, such as age and stress; however, little is known about the molecular genetic mechanisms that regulate this process. Immediate early genes of the Early growth response (Egr) family have critical roles in immune function and response to environmental stress. The transcription factors, Egr1, Egr2 and Egr3, play roles in the thymus and in peripheral T-cell activation. Nab2, which binds Egrs 1, 2, and 3 as a co-regulator of transcription, also regulates peripheral T-cell activation. However, a role for Nab2 in the thymus has not been reported. Using Nab2-deficient (KO) mice we found that male Nab2KO mice have reduced thymus size and decreased numbers of thymocytes, compared with age-matched wildtype (WT) mice. Furthermore, the number of thymocytes in Nab2KO males decreases more rapidly with age. This effect is sex-dependent as female Nab2KO mice show neither reduced thymocyte numbers nor accelerated thymocyte loss with age, compared to female WT littermates. Since stress induces expression of Nab2 and the Egrs, we examined whether loss of Nab2 alters stress-induced decrease in thymic cellularity. Restraint stress induced a significant decrease in thymic cellularity in Nab2KO and WT mice, with significant changes in the thymocyte subset populations only in the Nab2KO mice. Stress reduced the percentage of DP cells by half and increased the percentage of CD4SP and CD8SP cells by roughly three-fold in Nab2KO mice. These findings indicate a requirement for Nab2 in maintaining thymocyte number in male mice with age and in response to stress.
• Roe, D. J., Menon, H., Meador, L. R., Hastings, K. T., Dicaudo, D. J., & Cui, H. (2017). LB997 Inducers of GILT expression in human melanoma. Journal of Investigative Dermatology, 137(10), B12. doi:10.1016/j.jid.2017.07.079
• Nguyen, J., Bernert, R., In, K., Kang, P., Sebastiao, N., Hu, C., & Hastings, K. T. (2016). Gamma-interferon-inducible lysosomal thiol reductase is upregulated in human melanoma. Melanoma Research.
• Nguyen, J., Bernert, R., In, K., Kang, P., Sebastiao, N., Hu, C., & Hastings, K. T. (2016). Gamma-interferon-inducible lysosomal thiol reductase is upregulated in human melanoma. Melanoma research, 26(2), 125-37.
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  T-cell-mediated immunity has the ability to produce durable antimelanoma responses, resulting in improved survival of patients with advanced melanoma. Antigen presentation is a key determinant of T-cell responses. Gamma-interferon-inducible lysosomal thiol reductase (GILT) is critical for MHC class II-restricted presentation of multiple melanoma antigens to CD4+ T cells. However, GILT expression in melanoma has not been defined. We evaluated GILT and MHC class II expression in human primary and metastatic melanomas and nevi using immunohistochemical analysis. GILT staining in melanocytes was observed in 70% of primary and 58% of metastatic melanomas versus 0% of nevi. When present, the GILT staining intensity in melanocytes was typically faint. Both GILT and MHC class II expression were increased in melanocytes of primary and metastatic melanomas compared with nevi. GILT staining in antigen-presenting cells (APCs) was detected in 100% of primary and metastatic melanomas versus 31% of nevi, and it was typically intense. GILT expression was increased in APCs of primary and metastatic melanomas compared with nevi, whereas MHC class II had equivalent high expression in APCs of all melanocytic lesions. GILT staining in keratinocytes was detected in 67% of primary melanomas versus 14% of nevi and 6% of metastatic melanomas. GILT, but not MHC class II, expression was increased in keratinocytes of primary melanomas compared with nevi and metastases. GILT expression is anticipated to result in improved presentation of melanoma antigens and more effective antimelanoma T-cell responses. GILT expression may be a biomarker of immune recognition of melanoma.
• Waterfield, M., Rausch, M. P., Metzger, T. C., Hastings, K. T., Cortez, J. T., Anderson, M. S., & Anderson, A. (2016). 007 GILT-mediated antigen processing in thymic epithelial cells diminishes T cell-mediated protection from melanoma through promoting thymic deletion and regulatory T cells. Journal of Investigative Dermatology, 136(5), S2. doi:10.1016/j.jid.2016.02.031
• Rausch, M. P., & Hastings, K. T. (2015). An exhaustion-like phenotype constrains the activity of CD4+ T cells specific for a self and melanoma antigen. PloS one, 10(4), e0123332.
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  While the immune system has the capacity to recognize and destroy melanoma, tolerance mechanisms often hinder the development of effective anti-tumor immune responses. Since many melanoma antigens are self proteins expressed in normal melanocytes, self antigen exposure before tumor development can negatively impact the function of T cells specific for these self/tumor antigens. However, the contribution of self tolerance to anti-melanoma T cell dysfunction remains largely unexplored. We have previously described a TCR transgenic (Tg) mouse model in which T cells specific for the self/melanoma antigen, tyrosinase-related protein 1 (TRP1), develop in the presence of endogenous TRP1 expression (Ag+) and diminished antigen presentation due to the absence of gamma-interferon-inducible lysosomal thiol reductase (GILT-/-). We show that TRP1-specific T cells from these Ag+GILT-/-Tg mice do not protect from melanoma tumor growth, fail to induce autoimmune vitiligo, and undergo diminished proliferation compared to T cells from Ag-GILT+/+Tg mice. Despite an increased frequency of TRP1-specific Treg cells in Ag+GILT-/-Tg mice compared to Ag-GILT+/+Tg animals, Treg cell depletion only partially rescues the proliferative capacity of T cells from TRP1-expressing mice, suggesting the involvement of additional suppressive mechanisms. An increased percentage of melanoma-specific T cells from Ag+GILT-/-Tg animals express PD-1, an inhibitory receptor associated with the maintenance of T cell exhaustion. Antibody blockade of PD-1 partially improves the ability of TRP1-specific T cells from Ag+GILT-/-Tg mice to produce IL-2. These findings demonstrate that melanoma-specific T cells exposed to a self/melanoma antigen in healthy tissue develop an exhaustion-like phenotype characterized by PD-1-mediated immunosuppression prior to encounter with tumor.
• Rausch, M. P., & Hastings, K. T. (2015). Diverse cellular and organismal functions of the lysosomal thiol reductase GILT. Molecular immunology, 68(2 Pt A), 124-8.
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  Gamma-interferon-inducible lysosomal thiol reductase (GILT) is the only enzyme known to catalyze disulfide bond reduction in the endocytic pathway. GILT facilitates the presentation of a subset of epitopes from disulfide bond-containing antigens. Enhanced presentation of MHC class II-restricted epitopes alters central tolerance and modulates CD4+ T cell-mediated autoimmunity. Improved cross-presentation of viral epitopes results in improved cross-priming of viral-specific CD8+ T cells. GILT regulates the cellular redox state. In GILT-/- cells, there is a shift from the reduced to the oxidized form of glutathione, resulting in mitochondrial autophagy, decreased superoxide dismutase 2, and elevated superoxide levels. GILT expression diminishes cellular activation, including decreased phosphorylated ERK1/2, and decreases cellular proliferation. GILT enhances the activity of bacterial hemolysins, such as listeriolysin O, and increases bacterial replication and infection. GILT expression in cancer cells is associated with improved patient survival. These diverse roles of GILT are discussed.
• Waterfield, M., Rausch, M., Metzger, T. C., Hastings, K. T., Cortez, J. T., & Anderson, M. S. (2015). GILT-mediated processing of a self and melanoma antigen in thymic epithelial cells promotes deletion and regulatory T cells (APP3P.113). Journal of Immunology, 194.
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  Central tolerance is critical to prevent autoimmunity, but limits T cell responses to tumor Ag that are self Ag. We have identified that gamma-interferon-inducible lysosomal thiol reductase (GILT) is required for thymic deletion of CD4+ T cells specific for the self and melanoma Ag, tyrosinase-related protein 1 (TRP1). To define GILT’s role in central tolerance, we show that GILT expression is enriched in thymic APC capable of mediating deletion, medullary thymic epithelial cells (mTEC) and dendritic cells. TRP1 expression is restricted to mTEC. GILT facilitates MHC class II-restricted presentation of endogenous TRP1 by pooled thymic APC. Bone marrow (BM) chimeras demonstrate that GILT expression in TEC is necessary and sufficient for efficient deletion of TRP1-specific thymocytes. In chimeras that express GILT in TEC, TRP1-specific T cells undergo deletion, and chimeras are not protected from melanoma challenge. Although an intermediate level of TRP1-specific T cells develop in chimeras with GILT expression limited to BM-derived cells, only chimeras lacking GILT in both populations are protected from melanoma challenge. Chimeras that express GILT in TECs or in which GILT is limited to BM-derived cells have a substantially higher percentage of TRP1-specific regulatory T (Treg) cells and lower effector:Treg cell ratio. These findings suggest that GILT operates in mTEC to facilitate the presentation of tissue-specific self Ag and promote deletion and development of Treg cells.
• Hastings, K. T. (2013). GILT: Shaping the MHC Class II-Restricted Peptidome and CD4(+) T Cell-Mediated Immunity. Frontiers in immunology, 4, 429.
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  The MHC class II-restricted antigen processing pathway generates peptide:MHC complexes in the endocytic pathway for the activation of CD4(+) T cells. Gamma-interferon-inducible lysosomal thiol reductase (GILT) reduces protein disulfide bonds in the endocytic compartment, thereby exposing buried epitopes for MHC class II binding and presentation. T cell hybridoma responses and elution of MHC class II bound peptides have identified GILT-dependent epitopes, GILT-independent epitopes, and epitopes that are more efficiently presented in the absence of GILT termed GILT-prevented epitopes. GILT-mediated alteration in the MHC class II-restricted peptidome modulates T cell development in the thymus and peripheral tolerance and influences the pathogenesis of autoimmunity. Recent studies suggest an emerging role for GILT in the response to pathogens and cancer survival.
• Hastings, K., Hastings, K. T., Phipps-Yonas, H., & Semik, V. (2013). GILT expression in B cells diminishes cathepsin S steady-state protein expression and activity. European Journal of Immunology, 43(1), 65-74.
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  MHC class II-restricted Ag processing requires protein degradation in the endocytic pathway for the activation of CD4(+) T cells. Gamma-interferon-inducible lysosomal thiol reductase (GILT) facilitates Ag processing by reducing protein disulfide bonds in this compartment. Lysosomal cysteine protease cathepsin S (CatS) contains disulfide bonds and mediates essential steps in MHC class II-restricted processing, including proteolysis of large polypeptides and cleavage of the invariant chain. We sought to determine whether GILT's reductase activity regulates CatS expression and function. Confocal microscopy confirmed that GILT and CatS colocalized within lysosomes of B cells. GILT expression posttranscriptionally decreased the steady-state protein expression of CatS in primary B cells and B-cell lines. GILT did not substantially alter the expression of other lysosomal proteins, including H2-M, H2-O, or CatL. GILT's reductase active site was necessary for diminished CatS protein levels, and GILT expression decreased the half-life of CatS, suggesting that GILT-mediated reduction of protein disulfide bonds enhances CatS degradation. GILT expression decreased the proteolysis of a CatS selective substrate. This study illustrates a physiologic mechanism that regulates CatS and has implications for fine tuning MHC class II-restricted Ag processing and for the development of CatS inhibitors, which are under investigation for the treatment of autoimmune disease.
• Phipps-Yonas, H., Cui, H., Sebastiao, N., Brunhoeber, P. S., Haddock, E., Deymier, M. J., Klapper, W., Lybarger, L., Roe, D. J., & Hastings, K. T. (2013). Low GILT Expression is Associated with Poor Patient Survival in Diffuse Large B-Cell Lymphoma. Frontiers in immunology, 4, 425.
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  The major histocompatibility complex (MHC) class II-restricted antigen processing pathway presents antigenic peptides acquired in the endocytic route for the activation of CD4(+) T cells. Multiple cancers express MHC class II, which may influence the anti-tumor immune response and patient outcome. Low MHC class II expression is associated with poor survival in diffuse large B-cell lymphoma (DLBCL), the most common form of aggressive non-Hodgkin lymphoma. Therefore, we investigated whether gamma-interferon-inducible lysosomal thiol reductase (GILT), an upstream component of the MHC class II-restricted antigen processing pathway that is not regulated by the transcription factor class II transactivator, may be important in DLBCL biology. GILT reduces protein disulfide bonds in the endocytic compartment, exposing additional epitopes for binding to MHC class II and facilitating antigen presentation. In each of four independent gene expression profiling cohorts with a total of 585 DLBCL patients, low GILT expression was significantly associated with poor overall survival. In contrast, low expression of a classical MHC class II gene, HLA-DRA, was associated with poor survival in one of four cohorts. The association of low GILT expression with poor survival was independent of established clinical and molecular prognostic factors, the International Prognostic Index and the cell of origin classification, respectively. Immunohistochemical analysis of GILT expression in 96 DLBCL cases demonstrated variation in GILT protein expression within tumor cells which correlated strongly with GILT mRNA expression. These studies identify a novel association between GILT expression and clinical outcome in lymphoma. Our findings underscore the role of antigen processing in DLBCL and suggest that molecules targeting this pathway warrant investigation as potential therapeutics.
• Hastings, K., Hastings, K. T., & Rausch, M. P. (2012). GILT modulates CD4+ T-cell tolerance to the melanocyte differentiation antigen tyrosinase-related protein 1. Journal of Investigative Dermatology, 132(1).
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  Gamma-IFN-inducible lysosomal thiol reductase (GILT) facilitates major histocompatibility complex class II-restricted processing through endocytic reduction of protein disulfide bonds and is necessary for efficient class II-restricted processing of melanocyte differentiation antigen, tyrosinase-related protein 1 (TRP1). Using class II-restricted, TRP1-specific T-cell receptor transgenic mice, we identify a role, to our knowledge, previously unreported, for GILT in the maintenance of tolerance to TRP1. TRP1-specific thymocytes are centrally deleted in the presence of GILT and TRP1. In contrast, CD4 single-positive thymocytes and peripheral T cells develop in the absence of GILT or TRP1, demonstrating that GILT is required for negative selection of TRP1-specific thymocytes. Although TRP1-specific T cells escape thymic deletion in the absence of GILT, they are tolerant to TRP1 and do not induce vilitigo. TRP1-specific T cells that develop in the absence of GILT have diminished IL-2 and IFN-γ production. Furthermore, GILT-deficient mice have a 4-fold increase in the percentage of TRP1-specific regulatory T (Treg) cells compared with TRP1-deficient mice, and depletion of Treg cells partially restores the ability of GILT-deficient TRP1-specific CD4(+) T cells to induce vitiligo. Thus, GILT has a critical role in regulating CD4(+) T-cell tolerance to an endogenous skin-restricted antigen relevant to controlling autoimmunity and generating effective immunotherapy for melanoma.
• Rausch, M., & Hastings, K. T. (2012). GILT modulates CD4 + T cell tolerance to cutaneous autoantigen TRP1. Molecular Immunology, 51(1), 17. doi:10.1016/j.molimm.2012.02.043
• Hastings, K. T., & Cresswell, P. (2011). Disulfide reduction in the endocytic pathway: immunological functions of gamma-interferon-inducible lysosomal thiol reductase. Antioxidants & redox signaling, 15(3), 657-68.
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  Gamma-interferon-inducible lysosomal thiol reductase (GILT) is constitutively expressed in most antigen presenting cells and is interferon γ inducible in other cell types via signal transducer and activator of transcription 1. Normally, N- and C-terminal propeptides are cleaved in the early endosome, and the mature protein resides in late endosomes and lysosomes. Correspondingly, GILT has maximal reductase activity at an acidic pH. Monocyte differentiation via Toll-like receptor 4 triggers secretion of a disulfide-linked dimer of the enzymatically active precursor, which may contribute to inflammation. GILT facilitates major histocompatibility complex (MHC) class II-restricted processing through reduction of protein disulfide bonds in the endocytic pathway and is hypothesized to expose buried epitopes for MHC class II binding. GILT can also facilitate the transfer of disulfide-containing antigens into the cytosol, enhancing their cross-presentation by MHC class I. A variety of antigens are strongly influenced by GILT-mediated reduction, including hen egg lysozyme, melanocyte differentiation antigens, and viral envelope glycoproteins. In addition, GILT is conserved among lower eukaryotes and likely has additional functions. For example, GILT expression increases the stability of superoxide dismutase 2 and decreases reactive oxygen species, which correlates with decreased cellular proliferation. It is also a critical host factor for infection with Listeria monocytogenes.
• Rausch, M., Metzger, T. C., Hastings, K. T., & Anderson, M. S. (2011). GILT regulates CD4+ T cell tolerance. Journal of Immunology, 186.
• Semik, V., Phipps-yonas, H., & Hastings, K. T. (2011). Gamma-interferon-inducible lysosomal thiol reductase diminishes cathepsin S expression and function. Journal of Immunology, 186.
• Hastings, K. T., Hastings, K., Rausch, M. P., Irvine, K. R., Antony, P. A., Restifo, N. P., & Cresswell, P. (2010). GILT accelerates autoimmunity to the melanoma antigen tyrosinase-related protein 1. Journal of Immunology, 185(5).
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  Melanocyte differentiation Ags, including tyrosinase-related protein (TRP) 1, are relevant to both autoimmune skin depigmentation (vitiligo) and tumor immunity, because they are expressed by both benign melanocytes and many malignant melanomas. Melanoma patients generate CD4(+) T cells that specifically recognize these proteins. TRP1 contains internal disulfide bonds and is presented by MHC class II molecules. Gamma-IFN-inducible lysosomal thiol reductase (GILT) facilitates the generation of class II-binding peptides by the endocytic reduction of protein disulfide bonds. We show in this study that GILT is required for efficient MHC class II-restricted processing of a TRP1 epitope in vitro and accelerates the onset of vitiligo in TRP1-specific TCR transgenic mice. The presence of GILT confers a small increase in the percentage of autoreactive T cells with an effector memory phenotype that may contribute to earlier disease onset. The onset of vitiligo is associated with a greater increase in the percentage of autoreactive T cells with an effector memory phenotype. Given that many self and tumor Ags have disulfide bonds and are presented on MHC class II, GILT is likely to be important in the pathogenesis of other CD4(+) T cell-mediated autoimmune diseases and for the development of effective cancer immunotherapy.
• Hastings, K. T., Lackman, R. L., & Cresswell, P. (2006). Functional requirements for the lysosomal thiol reductase GILT in MHC class II-restricted antigen processing. Journal of immunology (Baltimore, Md. : 1950), 177(12), 8569-77.
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  Ag processing and presentation via MHC class II is essential for activation of CD4(+) T lymphocytes. gamma-IFN-inducible lysosomal thiol reductase (GILT) is present in the MHC class II loading compartment and has been shown to facilitate class II Ag processing and recall responses to Ags containing disulfide bonds such as hen egg lysozyme (HEL). Reduction of proteins within the MHC class II loading compartment is hypothesized to expose residues for class II binding and protease trimming. In vitro analysis has shown that the active site of GILT involves Cys(46) and Cys(49), present in a CXXC motif that shares similarity with the thioredoxin family. To define the functional requirements for GILT in MHC class II Ag processing, a GILT-deficient murine B cell lymphoma line was generated and stably transduced with wild-type and cysteine mutants of GILT. Intracellular flow cytometric, immunoblotting, and immunofluorescence analyses demonstrated that wild-type and mutant GILT were expressed and maintained lysosomal localization. Transduction with wild-type GILT reconstituted MHC class II processing of a GILT-dependent HEL epitope. Mutation of either Cys(46) or Cys(49) abrogated MHC class II processing of a GILT-dependent HEL epitope. In addition, biochemical analysis of these mutants suggested that the active site facilitates processing of precursor GILT to the mature form. Precursor forms of GILT-bearing mutations in Cys(200) or Cys(211), previously found to display thiol reductase activity in vitro, could not mediate Ag processing. These studies demonstrate that the thiol reductase activity of GILT is its essential function in MHC class II-restricted Ag processing.
• Chavel, S., Hastings, K. T., Schaffer, J. V., Lazova, R., & Schechner, J. S. (2004). Calciphylaxis associated with acute, reversible renal failure in the setting of alcoholic cirrhosis. Journal of the American Academy of Dermatology, 5(50), S125-S128.

Presentations

• Hastings, K. T. (2021, Feb). Variable GILT protein expression in melanoma cells of metastatic tumor specimens. Experimental Biology Annual Meeting.
• Hastings, K. T. (2021, Mar). Role of GILT and MHC class II in melanoma cells on regulating the anti-tumor immune response. 16th Annual Frontiers in Immunobiology and Immunopathogenesis Symposium. Tucson.
• Hastings, K. T. (2021, May). Penalized regression analysis identifies features of the peptide:MHC class I interaction and mRNA expression as key to prioritizing neoantigen immunogenecity. Annual Meeting of the American Association of Immunologists.
• Hastings, K. T. (2021, May). Solar simulated light induces cutaneous SCC in inbred mouse strains: a clinically relevant model to investigate T cell responses model.. Annual Meeting of the Society for Investigative Dermatology.
• Hastings, K. T. (2020, May). GILT in thymic epithelial cells facilitates central CD4 T cell tolerance to a tissue-restricted, melanoma-associated self antigen. Annual Meeting of the American Association of Immunologists.
• Hastings, K. T. (2020, May). Solar simulated light induces cutaneous SCC in inbred mouse strains: development of a clinically relevant mouse model.. Annual Meeting of the Society for Investigative Dermatology.
• Hastings, K. T. (2019, February). High GILT expression and an active and functional MHC class II antigen presentation pathway are associated with improved survival in melanoma. Keystone Symposium on Uncovering mechanisms of immune-based therapy in cancer and autoimmunity. Breckenridge, CO.
• Hastings, K. T. (2019, May). High GILT expression and an active and intact MHC class II antigen presentation pathway are associated with improved survival in melanoma. Annual Meeting of the American Association of Immunologists. San Diego, CA.
• Meador, L. R., Rausch, M. P., Phipps-Yonas, H., Menon, H., & Hastings, K. T. (2017, December). Promoting enhanced T cell-mediated immunity to skin cancer. Arizona Wellbeing Commons, Viruses, Immunity, Microbiome and Infectious Disease Division. Tempe, AZ.
• Rausch, M. P., Metzger, T. C., Waterfield, M., Cortez, J., Anderson, M. S., & Hastings, K. T. (2016, August). GILT-mediated processing of a self and melanoma antigen in thymic epithelial cells promotes deletion and regulatory T cells. International Congress of Immunology. Melbourne, Australia.
• Nguyen, J., Bernert, R., In, K., Kang, P., Sebastiao, N., Hu, C., & Hastings, K. T. (2015, Winter). Gamma-interferon-inducible lysosomal thiol reductase is upregulated in human melanoma. Molecular and Cellular Biology and Microbiology Graduate Program Retreat. Tempe, AZ.
• Nguyen, J., Bernert, R., Ko, C., Sebastiao, N., Hu, C., & Hastings, K. T. (2015, March). Gamma-interferon-inducible lysosomal thiol reductase is upregulated in human melanoma. American Academy of Dermatology Annual Meeting. San Francisco, CA.
• Rausch, M. P., Metzger, T. C., Waterfield, M., Cortez, J., Anderson, M. S., & Hastings, K. T. (2015, March). GILT-mediated processing of a self and melanoma antigen in thymic epithelial cells promotes deletion and regulatory T cells. 10th Annual Frontiers in Immunobiology and Immunopathogenesis Symposium. Tucson.
• Rausch, M. P., Metzger, T. C., Waterfield, M., Cortez, J., Anderson, M. S., & Hastings, K. T. (2015, May). GILT-mediated processing of a self and melanoma antigen in thymic epithelial cells promotes deletion and regulatory T cells. American Association of Immunologists Annual Meeting. New Orleans, LA.
• Rausch, M. P., Metzger, T. C., Waterfield, M., Cortez, J., Anderson, M. S., & Hastings, K. T. (2015, May). GILT-mediated processing of a self and melanoma antigen in thymic epithelial cells promotes deletion and regulatory T cells. Society for Investigative Dermatology Annual Meeting. Atlanta, GA.
• Rausch, M. P., Metzger, T. C., Anderson, M. S., & Hastings, K. T. (2014, Summer). GILT expression in medullary thymic epithelial cells is required for presentation of tissue-specific self antigens and deletion of autoreactive T cells. 8th International Workshop on Antigen Processing and Presentation. Philadelphia, PA.
• Rausch, M., Metzger, T., Anderson, M., & Hastings, K. T. (2013, Spring). GILT expression in medullary thymic epithelial cells is required for presentation of tissue-specific self antigens and deletion of autoreactive T cells.. 100th Annual Meeting of the American Association of Immunologists. Honolulu, HI.
• Rausch, M., Metzger, T., Anderson, M., & Hastings, K. T. (2013, Spring). GILT expression in medullary thymic epithelial cells is required for presentation of tissue-specific self antigens and deletion of autoreactive T cells.. International Investigative Dermatology Meeting. Edinburgh, Scotland.
• Hastings, K. T. (2012, Spring). Immune recognition of melanoma and the role of MHC class II-restricted antigen processing components in melanoma and lymphoma.. Arizona Cancer Center Skin Cancer Institute and Ventana Medical Systems Scientific Retreat. Tucson, AZ.
• Rausch, M. P., & Hastings, K. T. (2012, Spring). CD4+ T cell tolerance to melanocyte differentiation antigen TRP1.. Society for Investigative Dermatology Annual Meeting. Raleigh, NC.
• Rausch, M. P., & Hastings, K. T. (2012, Spring). GILT modulates CD4+ T cell tolerance to cutaneous autoantigen TRP1.. 99th Annual Meeting of the American Association of Immunologists. Boston, MA..
• Rausch, M. P., Metzger, T. C., Anderson, M. S., & Hastings, K. T. (2012, Spring). GILT modulates CD4+ T cell tolerance to cutaneous autoantigen TRP1.. 7th International Antigen Processing and Presentation Workshop. Amsterdam, Netherlands.
• Phipps-Yonas, H. C., Semik, V., & Hastings, K. T. (2011, Spring). Gamma-interferon-inducible lysosomal thiol reductase diminishes cathepsin S expression and function.. 98th Annual Meeting of the American Association of Immunologists. San Francisco, CA.
• Rausch, M. P., Metzger, T. C., Anderson, M. S., & Hastings, K. T. (2011, Spring). GILT Regulates CD4+ T cell Tolerance. 98th Annual Meeting of the American Association of Immunologists. San Francisco, CA..
• Rausch, M. P., Metzger, T. C., Anderson, M. S., & Hastings, K. T. (2011, Spring). GILT modulates CD4+ T cell tolerance to the melanoma antigen TRP1.. 6th Annual Frontiers in Immunobiology and Immunopathogenesis Symposium. Tucson, AZ.
• Rausch, M. P., Metzger, T. C., Hastings, K. T., & Anderson, M. S. (2011, Spring). GILT modulates CD4+ T cell tolerance to the melanoma antigen TRP1.. Society for Investigative Dermatology Annual Meeting. Phoenix, AZ.
• Hastings, K. T. (2010, Spring). GILT modulates the development and function of CD4+ T specific for melanoma antigen TRP1.. 6th International Antigen Processing and Presentation Workshop. Corsica, France.
• Rausch, M. P., Semik, V., Anderson, M. S., Metzger, T. C., & Hastings, K. T. (2010, Spring). GILT modulates CD4+ T cell tolerance to the melanoma antigen TRP1. Cancer Research Institute's 18th Annual International Cancer Immunotherapy Symposium, Multiple Functions of CD4 T Cells in Autoimmunity, Infectious Disease, and Cancer. New York, NY.
• Rausch, M. P., Semik, V., Antony, P. A., Irvine, K. R., Restifo, N. P., Cresswell, P., & Hastings, K. T. (2010, Spring). GILT accelerates autoimmunity to melanoma antigen TRP1 and modulates CD4+ T cell development and function.. Keystone Symposium on Tolerance and Autoimmunity. Taos, NM.
• Hastings, K. T., Antony, P. A., Irvine, K. R., Restifo, N. P., & Cresswell, P. (2009, Spring). Lysosomal thiol reductase GILT is important in immune recognition of melanoma antigen TRP1.. Keystone Symposium on Mobilizing Cellular Immunity for Cancer Therapy. Snowbird, UT.
• Rausch, M. P., Campbell, V., Antony, P. A., Irvine, K. R., Restifo, N. P., Cresswell, P., & Hastings, K. T. (2009, Spring). Role of lysosomal thiol reductase GILT in immune recognition of melanoma antigen TRP1. 7th World Congress on Melanoma. Vienna, Austria.
• Hastings, K. T. (2008, Spring). Lysosomal thiol reductase GILT is essential for MHC class II-restricted processing of melanoma antigen TRP1.. Cancer Immunology & Immunotherapy Realizing the Promise, National Cancer Institute. Bethesda, MD.
• Hastings, K. T., Irvine, K. R., Antony, P. A., Restifo, N. P., & Cresswell, P. (2008, Spring). Lysosomal thiol reductase GILT is essential for MHC class II-restricted processing of melanoma antigen TRP-1.. 3rd Annual Frontiers in Immunobiology and Immunopathogenesis Symposium. Tucson, AZ.
• Hastings, K. T., Irvine, K. R., Antony, P. A., Restifo, N. P., & Cresswell, P. (2008, Spring). Lysosomal thiol reductase GILT is essential for MHC class II-restricted processing of melanoma antigen TRP1.. International Investigative Dermatology Meeting. Kyoto, Japan.
• Hastings, K. T., Irvine, K. R., Antony, P. A., Restifo, N. P., & Cresswell, P. (2007, Spring). Lysosomal thiol reductase GILT is essential for MHC class II-restricted processing of melanoma antigen TRP1.. Society for Investigative Dermatology Annual Meeting. Los Angeles, CA.
• Hastings, K. T., Irvine, K. R., Antony, P. A., Restifo, N. P., & Cresswell, P. (2006, Spring). GILT is essential for MHC class II processing of melanocyte differentiation antigen TRP1.. Keystone Symposium on Advances in Melanoma. Sante Fe, NM.
• Hastings, K. T., Irvine, K. R., Antony, P. A., Restifo, N. P., & Cresswell, P. (2006, Spring). Lysosomal thiol reductase GILT is essential for MHC class II-restricted processing of melanoma antigen TRP-1.. BIO5 Institute Grand Opening. University of Arizona, Tucson, AZ.

Poster Presentations

• Hastings, K. T. (2021, April). NeoScore prioritizes immunogenic neoantigens and is associated with response to immune checkpoint inihbition. Cancer Research: Present & Future, University of Arizona Cancer Center. Tucson (virtual).
• Hastings, K. T. (2021, April). Role of GILT in melanoma cells on regulating in vivo tumor growth. Cancer Research: Present & Future, University of Arizona Cancer Center. Tucson (virtual).
• Hastings, K. T. (2021, April). Solar simulated light induces cutaneous SCC in inbred mice: a clinical relevant model to investigate T cell responses. Cancer Research: Present & Future, University of Arizona Cancer Center. Tucson (virtual).
• Hastings, K. T. (2021, Feb). Natural product-based induction of cancer cell death combined with immunotherapy for melanoma treatment. 6th Annual Arizona Biomedical Research Commission – Flinn Research Conference. Phoenix.
• Hastings, K. T. (2021, Feb). Role of GILT and MHC class II in melanoma cells on regulating the anti-tumor immune response. 6th Annual Arizona Biomedical Research Commission – Flinn Research Conference. Phoenix.
• Hastings, K. T. (2021, Mar). Solar simulated light induces cutaneous SCC in inbred mice: a clinically relevant model to investigate T cell responses. 16th Annual Frontiers in Immunobiology and Immunopathogenesis Symposium. Tucson.
• Hastings, K. T. (2020, Dec). Development of a clinically relevant cutaneous squamous cell carcinoma murine model. American Physician Scientist Association Western Regional Annual Meeting.
• Hastings, K. T. (2020, Dec). Predicted immune recognition of cutaneous squamous cell carcinoma decreased by low expression of neoantigens and MHC class I. American Physician Scientist Association Western Regional Annual Meeting.
• Hastings, K. T. (2020, Feb). High GILT expression and an active and intact MHC class II antigen presentation pathway are associated with improved survival in melanoma.. 5th Annual Arizona Biomedical Research Commission – Flinn Research Conference. Phoenix.
• Hastings, K. T. (2020, Feb). Natural products-based induction of cancer cell death combined with immunotherapy for melanoma treatment. 5th Annual Arizona Biomedical Research Commission – Flinn Research Conference. Phoenix.
• Hastings, K. T. (2020, Mar). Characterization of GILT and MHC class II in murine melanoma cell lines for determination of the role of the MHC class II pathway in melanoma cells. 15th Annual Frontiers in Immunobiology and Immunopathogenesis Symposium. Tucson.
• Borden, E. S., Kang, P., Natri, H. M., Phung, T. N., Wilson, M. A., Buetow, K. H., & Hastings, K. T. (2019, November). Neoantigen Fitness Model Predicts Lower Immune Recognition of Cutaneous Squamous Cell Carcinomas Than Actinic Keratoses. Reimagine Health: is my fate in my genes?. Phoenix, AZ: University of Arizona College of Medicine Phoenix.
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  A low percentage of actinic keratoses progress to develop into cutaneous squamous cell carcinoma. The immune mechanisms that successfully control or eliminate the majority of actinic keratoses and the mechanisms of immune escape by invasive squamous cell carcinoma are not well-understood. Here, we took a systematic approach to evaluate the neoantigens present in actinic keratosis and cutaneous squamous cell carcinoma specimens. We compared the number of mutations, the number of neoantigens predicted to bind MHC class I, and the number of neoantigens that are predicted to bind MHC class I and be recognized by a T cell receptor in actinic keratoses and cutaneous squamous cell carcinomas. We also considered the relative binding strengths to both MHC class I and the T cell receptor in a fitness cost model that allows for a comparison of the immune recognition potential of the neoantigens in actinic keratosis and cutaneous squamous cell carcinoma samples. The fitness cost was subsequently adjusted by the expression rates of the neoantigens to examine the role of neoantigen expression in tumor immune evasion. Our analyses indicate that, while the number of mutations and neoantigens are not significantly different between actinic keratoses and cutaneous squamous cell carcinomas, the predicted immune recognition of the neoantigen with the highest expression-adjusted fitness cost is lower for cutaneous squamous cell carcinomas compared with actinic keratoses. These findings suggest a role for the down-regulation of expression of highly immunogenic neoantigens in the immune escape of cutaneous squamous cell carcinomas. Furthermore, these findings highlight the importance of incorporating additional factors, such as the quality and expression of the neoantigens, rather than focusing solely on tumor mutational burden, in assessing immune recognition potential.
• Hastings, K. T. (2019, March). High GILT expression and an active and functional MHC class II antigen presentation pathway are associated with improved survival in melanoma. Keystone Symposium on Cancer Immunotherapy: mechanistic insights to improved clinical benefit. Whistler, British Columbia, Canada.
• Hastings, K. T. (2019, May). High GILT expression and an active and intact MHC class II antigen presentation pathway are associated with improved survival in melanoma. 4th Annual Arizona Biomedical Research Commission Conference. Phoenix.
• Hastings, K. T. (2018, May). GILT in thymic epithelial cells preferentially facilitates MHC class II-restricted presentation in generating central tolerance to a self and melanoma antigen.. Annual Meeting of the American Association of Immunologists. Austin, TX.
• Hastings, K. T. (2018, May). Inflammation induces GILT expression in human melanoma.. Annual Meeting of the American Association of Immunologists. Austin, TX.
• Cole, L. S., Kang, P., & Hastings, K. T. (2017, March). Primary melanoma tumor immune contexture analysis. Scholarly Project Student Research Symposium. Phoenix, AZ: University of Arizona College of Medicine Phoenix.
• Johnson, K., & Hastings, K. T. (2017, March). Cross-presentation of gp100 melanoma antigen. Frontiers in Immunobiology and Immunopathogenesis Symposium. Tucson, AZ: University of Arizona College of Medicine Tucson.
• Johnson, K., & Hastings, K. T. (2017, March). Cross-presentation of gp100 melanoma antigen. Scholarly Project Student Research Symposium. Phoenix, AZ: University of Arizona College of Medicine Phoenix.
• Meador, L. R., Menon, H., Thomson, N., Cui, H., Roe, D., Homsi, J., & Hastings, K. T. (2017, March). Evaluating the association of GILT expression with patient outcome in metastatic melanoma. 2nd Annual Arizona Biomedical Research Commission Research Conference. Phoenix, AZ.
• Meador, L. R., Menon, H., Thomson, N., Cui, H., Roe, D., Homsi, J., & Hastings, K. T. (2017, March). Evaluating the association of GILT expression with patient outcome in metastatic melanoma. AZBio Expo in partnership with National Institue of Collaborative Healthcare. Tempe, AZ.
• Meador, L. R., Rausch, M. P., Phipps-Yonas, H., Menon, H., & Hastings, K. T. (2017, October). Promoting enhanced T cell-mediated immunity to skin cancer. University of Arizona Cancer Center Scientific Symposium. Phoenix, AZ.
• Meador, L. R., Rausch, M. P., Phipps-Yonas, H., Menon, H., & Hastings, K. T. (2017, September). Promoting enhanced T cell-mediated immunity to skin cancer. Arizona Wellbeing Commons. Tempe, AZ.
• Menon, H., DiCaudo, D. J., & Hastings, K. T. (2017, March). Inducers of GILT expression in human melanoma. Scholarly Project Student Research Symposium. Phoenix, AZ: University of Arizona College of Medicine Phoenix.
• Menon, H., Meador, L. R., Cui, H., Roe, D., DiCaudo, D. J., & Hastings, K. T. (2017, May). Inducers of GILT expression in human melanoma. Society for Investigative Dermatology Annual Meeting. Portland, OR.
• Rausch, M. P., Meador, L. R., Metzger, T. C., Anderson, M. S., & Hastings, K. T. (2017, December). Thymic GILT promotes central tolerance and limits anti-tumor immunity. Arizona Wellbeing Commons, Viruses, Immunity, Microbiome and Infectious Disease Division. Tempe.
• Rausch, M. P., Meador, L. R., Metzger, T. C., Anderson, M. S., & Hastings, K. T. (2017, October). Thymic GILT promotes central tolerance and limits anti-tumor immunity. University of Arizona Cancer Center Scientific Symposium. Phoenix.
• Rausch, M. P., Meador, L. R., Metzger, T. C., Anderson, M. S., & Hastings, K. T. (2017, September). Thymic GILT promotes central tolerance and limits anti-tumor immunity. Arizona Wellbeing Commons. Tempe.
• In, K., In, K., Menon, H., Menon, H., Nguyen, J., Nguyen, J., Sebastiao, N., Sebastiao, N., Kang, P., Kang, P., Hu, C., Hu, C., Bernert, R., Bernert, R., DiCaudo, D. J., DiCaudo, D. J., Hastings, K. T., & Hastings, K. T. (2016, May). Gamma-interferon-inducible lysosomal thiol reductase is upregulated in human melanoma. Society for Investigative Dermatology Annual Meeting. Phoenix, AZ.
• In, K., In, K., Nguyen, J., Nguyen, J., Bernert, R., Bernert, R., Kang, P., Kang, P., Sebastiao, N., Sebastiao, N., Hu, C., Hu, C., Hastings, K. T., & Hastings, K. T. (2016, March). Gamma-interferon-inducible lysosomal thiol reductase is upregulated in human melanoma. 11th Annual Frontiers in Immunobiology and Immunopathogenesis Symposium. Tucson, AZ.
• In, K., Menon, H., Nguyen, J., Sebastiao, N., Kang, P., Hu, C., Bernert, R., DiCaudo, D. J., & Hastings, K. T. (2016, August). Gamma-interferon-inducible lysosomal thiol reductase is upregulated in human melanoma. Internationa Congress of Immunology. Melbourne, Australia.
• Menon, H., In, K., Kang, P., DiCaudo, D. J., & Hastings, K. T. (2016, March). Gamma-interferon-inducible lysosomal thiol reductase is upregulated in inflamed nevi. 11th Annual Frontiers in Immunobiology and Immunopathogenesis Symposium. Tucson, AZ.
• Rausch, M. P., Metzger, T. C., Waterfield, M., Cortez, J., Anderson, M. S., & Hastings, K. T. (2016, May). GILT-mediated processing of a self and melanoma antigen in thymic epithelial cells promotes deletion and regulatory T cells. Society for Investigative Dermatology Annual Meeting. Phoenix, AZ.
• Nguyen, J., Bernert, R., Ko, C., Sebastiao, N., Hu, C., & Hastings, K. T. (2015, March). Gamma-interferon-inducible lysosomal thiol reductase is upregulated in human melanoma. 10th Annual Frontiers in Immunobiology and Immunopathogenesis Symposium. Tucson, AZ.
• Nguyen, J., Bernert, R., Ko, C., Sebastiao, N., Hu, C., & Hastings, K. T. (2015, May). Gamma-interferon-inducible lysosomal thiol reductase is upregulated in human melanoma. American Association of Immunologists. New Orleans, LA.
• Rausch, M. P., & Hastings, K. T. (2014, Spring). Multiple peripheral tolerance mechanisms constrain the activity of CD4+ T cells specific for the melanocyte differentiation antigen tyrosinase-related protein 1. 9th Annual Frontiers in Immunobiology and Immunopathogenesis Symposium, Tucson, AZ.. Tucson, AZ.
• Phipps-Yonas, H., Cui, H., Haddock, E., Deymier, M. J., Lybarger, L., Roe, D. J., & Hastings, K. T. (2013, Spring). Low GILT expression is associated with poor survival in diffuse large B-cell lymphoma.. 100th Annual Meeting of the American Association of Immunologists. Honolulu, HI.
• Phipps-Yonas, H., Cui, H., Haddock, E., Deymier, M. J., Lybarger, L., Roe, D. J., & Hastings, K. T. (2013, Spring). Low GILT expression is associated with poor survival in diffuse large B-cell lymphoma.. 8th Annual Frontiers in Immunobiology and Immunopathogenesis Symposium. Tucson, AZ.
• Phipps-Yonas, H., Cui, H., Sebastiao, N., Brunhoeber, P. S., Deymier, M. J., Lybarger, L., Klapper, W., Roe, D. J., & Hastings, K. T. (2013, Spring). Low GILT expression is associated with poor survival in diffuse large B-cell lymphoma. AZBio Expo, Arizona Bioindustry Association. Tempe, AZ.
• Rausch, M. P., Metzger, T. C., Anderson, M. S., & Hastings, K. T. (2013, Spring). GILT expression in medullary thymic epithelial cells is required for presentation of tissue-specific self antigens and deletion of autoreactive T cells.. 8th Annual Frontiers in Immunobiology and Immunopathogenesis Symposium. Tucson, AZ.
• Haddock, E., & Hastings, K. T. (2012, Spring). Histological analysis of murine skin.. 7th Annual Frontiers in Immunobiology and Immunopathogenesis Symposium. Tucson, AZ.
• Phipps-Yonas, H., Cui, H., Haddock, E., Deymier, M., Lybarger, L., Rimsza, L. M., Roe, D. J., & Hastings, K. T. (2012, Spring). Loss of GILT expression predicts poor prognosis in diffuse large B-cell lymphoma.. 7th Annual Frontiers in Immunobiology and Immunopathogenesis Symposium. Tucson, AZ.
• Rausch, M. P., & Hastings, K. T. (2012, Spring). GILT modulates CD4+ T cell tolerance to the cutaneous autoantigen TRP1.. 7th Annual Frontiers in Immunobiology and Immunopathogenesis Symposium. Tucson, AZ.
• Phipps-Yonas, H. C., Semik, V., & Hastings, K. T. (2011, Spring). Gamma-interferon-inducible lysosomal thiol reductase diminishes cathepsin S expression and function.. 6th Annual Frontiers in Immunobiology and Immunopathogenesis Symposium. Tucson, AZ.
• Rausch, M. P., Semik, V., Antony, P. A., Irvine, K. R., Restifo, N. P., Cresswell, P., & Hastings, K. T. (2010, Spring). GILT accelerates autoimmunity to melanoma antigen TRP1 and modulates CD4+ T cell development and function.. 5th Annual Frontiers in Immunobiology and Immunopathogenesis Symposium. Tucson, AZ.
• Semik, V., Phipps-Yonas, H. C., & Hastings, K. T. (2010, Spring). GILT modulates MHC class II-restricted antigen processing by decreasing cathepsin S expression and function.. 5th Annual Frontiers in Immunobiology and Immunopathogenesis Symposium. Tucson, AZ.
• Hastings, K. T., Rausch, M. P., Antony, P. A., Irvine, K. R., Restifo, N. P., & Cresswell, P. (2009, Spring). Lysosomal thiol reductase GILT is important in immune recognition of melanoma antigen TRP1.. 4th Annual Frontiers in Immunobiology and Immunopathogenesis Symposium. Tucson, AZ.
• Semik, V., & Hastings, K. T. (2009, Spring). GILT expression alters the MHC class II loading compartment.. 4th Annual Frontiers in Immunobiology and Immunopathogenesis Symposium. Tucson, AZ.
• Semik, V., & Hastings, K. T. (2009, Spring). GILT expression alters the MHC class II loading compartment.. Translational Genomics Research Institute Scientific Retreat. Phoenix, AZ.
• Hastings, K. T., Irvine, K. R., Antony, P. A., Restifo, N. P., & Cresswell, P. (2008, Spring). Lysosomal thiol reductase GILT is essential for MHC class II-restricted processing of melanoma antigen TRP-1.. Translational Genomics Research Institute Scientific Retreat. Phoenix, AZ.

Others

• Girardi, M., & Hastings, K. T. (2006, Spring). Update on cutaneous T-cell lymphoma: pathogenesis and therapy; DermQuest Thought Leader Commentary.
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  Electronic PublicationResearch Update (www.dermquest.com)