Jose Alejandro Guevara, MD, PhD

Dr. Guevara-Patiño’s research is focused on identifying signaling cues that can be exploited for the benefit of cancer patients receiving T cell-based immunotherapy, by deeply understanding the immune fertile conditions that are necessary to generate robust anti-tumor T cell responses. José Alejandro is specifically interested in understanding the role of RPS6 as well as the effects of tumor-related hypoxia on anti-tumor T cells. In addition, he is implementing machine learning approaches for the development of immunological predictive biomarkers that will permit the stratification of cancer patients receiving immunotherapies.

Associations

• Immunology
• Immuno-Oncology Program

Education & Training

Graduate:

• University College London, National Institute for Medical Research, UK, PhD - Immunology

Fellowship:

• Memorial Sloan-Kettering Cancer Center - T Cell Development and tumor Immunology

Medical School:

• Universidad Central de Venezuela - MD

Dr. Guevara-Patiño’s research is focused on identifying signaling cues that can be exploited for the benefit of cancer patients receiving T cell-based immunotherapy, by deeply understanding the immune fertile conditions that are necessary to generate robust anti-tumor T cell responses. José Alejandro is specifically interested in understanding the role of RPS6 as well as the effects of tumor-related hypoxia on anti-tumor T cells. In addition, he is implementing machine learning approaches for the development of immunological predictive biomarkers that will permit the stratification of cancer patients receiving immunotherapies.

• Perez C, Plaza-Rojas L, Boucher JC, Nagy MZ, Kostenko E, Prajapati K, Burke B, Reyes MD, Austin AL, Zhang S, Le PT, Guevara-Patino JA. NKG2D receptor signaling shapes T cell thymic education. J Leukoc Biol. 2024 Jan.115(2):306-321. Pubmedid: 37949818.
• Chaudhary R, Slebos RJC, Noel LC, Song F, Poole MI, Hoening DS, Hernandez-Prera JC, Conejo-Garcia JR, Guevara-Patino JA, Wang X, Xie M, Tan AC, Chung CH. EGFR Inhibition by Cetuximab Modulates Hypoxia and IFN Response Genes in Head and Neck Squamous Cell Carcinoma. Cancer Res Commun. 2023 May.3(5):896-907. Pubmedid: 37377902. Pmcid: PMC10202124.
• Jain RK, Singh AM, Wang X, Guevara-Patiño JA, Sonpavde G. Emerging monoclonal antibody therapies in the treatment of metastatic urothelial carcinoma. Expert Opin Emerg Drugs. 2023 Mar.28(1):17-26. Pubmedid: 36882977.
• Kohlhapp FJ, O'Sullivan JA, Moore TV, Zloza A, Guevara-Patiño JA. NKG2D signaling shifts the balance of CD8 T cells from single cytokine- to polycytokine-producing effector cells. Mol Immunol. 2023 Mar.155:1-6. Pubmedid: 36634520. Pmcid: PMC9992161.
• Jhawar SR, Wang SJ, Thandoni A, Bommareddy PK, Newman JH, Marzo AL, Kuzel TM, Gupta V, Reiser J, Daniels P, Schiff D, Mitchell D, LeBoeuf NR, Simmons C, Goyal S, Lasfar A, Guevara-Patino JA, Haffty BG, Kaufman HL, Silk AW, Zloza A. Combination oncolytic virus, radiation therapy, and immune checkpoint inhibitor treatment in anti-PD-1-refractory cancer. J Immunother Cancer. 2023 Jul.11(7). Pubmedid: 37433716. Pmcid: PMC10347455.
• Singh AM, Guevara-Patino JA, Wang X, Li R, Sonpavde G, Jain RK. Antibody-Drug Conjugates in the Treatment of Urothelial Cancer. BioDrugs. 2023 Jul.37(4):505-520. Pubmedid: 37256534.
• O'Sullivan JA, Kohlhapp FJ, Zloza A, Plaza-Rojas L, Burke B, Dulin NO, Guevara-Patiño JA. Memory Precursors and Short-Lived Effector T cell Subsets Have Different Sensitivities to TGFβ. Int J Mol Sci. 2023 Feb.24(4). Pubmedid: 36835342. Pmcid: PMC9966622.
• Boucher JC, Shrestha B, Vishwasrao P, Leick M, Cervantes EV, Ghafoor T, Reid K, Spitler K, Yu B, Betts BC, Guevara-Patino JA, Maus MV, Davila ML. Bispecific CD33/CD123 targeted chimeric antigen receptor T cells for the treatment of acute myeloid leukemia. Mol Ther Oncolytics. 2023 Dec.31:100751. Pubmedid: 38075241. Pmcid: PMC10701585.
• Conejo-Garcia JR, Guevara-Patino JA. Barriers and Opportunities for CAR T-Cell Targeting of Solid Tumors. Immunol Invest. 2022 Nov.51(8):2215-2225. Pubmedid: 35797428. Pmcid: PMC9795814.
• Wang X, Muzaffar J, Kirtane K, Song F, Johnson M, Schell MJ, Li J, Yoder SJ, Conejo-Garcia JR, Guevara-Patino JA, Bonomi M, Bhateja P, Rocco JW, Steuer CE, Saba NF, Chung CH. T cell repertoire in peripheral blood as a potential biomarker for predicting response to concurrent cetuximab and nivolumab in head and neck squamous cell carcinoma. J Immunother Cancer. 2022 Jun.10(6). Pubmedid: 35676062. Pmcid: PMC9185557.
• Rossi M, Aspromonte SM, Kohlhapp FJ, Newman JH, Lemenze A, Pepe RJ, DeFina SM, Herzog NL, Donnelly R, Kuzel TM, Reiser J, Guevara-Patino JA, Zloza A. Gut Microbial Shifts Indicate Melanoma Presence and Bacterial Interactions in a Murine Model. Diagnostics (Basel). 2022 Apr.12(4). Pubmedid: 35454006. Pmcid: PMC9029337.
• Jaishankar D, Cosgrove C, Ramesh P, Mahon J, Shivde R, Dellacecca ER, Yang SF, Mosenson J, Guevara-Patiño JA, Le Poole IC. HSP70iQ435A to subdue autoimmunity and support anti-tumor responses. Cell Stress Chaperones. 2021 Sep.26(5):845-857. Pubmedid: 34542825. Pmcid: PMC8492854.
• Plaza-Rojas L, Guevara-Patiño JA. Corrigendum: The Role of NKG2D in Vitiligo. Front Immunol. 2021 Jun.12:714137. Pubmedid: 34177971. Pmcid: PMC8221182.
• Plaza-Rojas L, Guevara-Patiño JA. The Role of the NKG2D in Vitiligo. Front Immunol. 2021 Feb.12:624131. Pubmedid: 33717132. Pmcid: PMC7952755.
• Guevara-Patiño JA, Plaza-Rojas L. It Takes Two to Tango. J Invest Dermatol. 2020 Jun.140(6):1131-1133. Pubmedid: 32446332.
• Perez C, Prajapati K, Burke B, Plaza-Rojas L, Zeleznik-Le NJ, Guevara-Patino JA. NKG2D signaling certifies effector CD8 T cells for memory formation. J Immunother Cancer. 2019 Feb.7(1):48. Pubmedid: 30777125. Pmcid: PMC6380053.
• Prajapati K, Perez C, Rojas LBP, Burke B, Guevara-Patino JA. Functions of NKG2D in CD8+ T cells: an opportunity for immunotherapy. Cell Mol Immunol. 2018 May.15(5):470-479. Pubmedid: 29400704. Pmcid: PMC6068164.
• Henning SW, Fernandez MF, Mahon JP, Duff R, Azarafrooz F, Guevara-Patiño JA, Rademaker AW, Salzman AL, Le Poole IC. HSP70iQ435A-Encoding DNA Repigments Vitiligo Lesions in Sinclair Swine. J Invest Dermatol. 2018 Dec.138(12):2531-2539. Pubmedid: 30031029. Pmcid: PMC9732057.
• Kohlhapp FJ, Huelsmann EJ, Lacek AT, Schenkel JM, Lusciks J, Broucek JR, Goldufsky JW, Hughes T, Zayas JP, Dolubizno H, Sowell RT, Kühner R, Burd S, Kubasiak JC, Nabatiyan A, Marshall S, Bommareddy PK, Li S, Newman JH, Monken CE, Shafikhani SH, Marzo AL, Guevara-Patino JA, Lasfar A, Thomas PG, Lattime EC, Kaufman HL, Zloza A. Non-oncogenic Acute Viral Infections Disrupt Anti-cancer Responses and Lead to Accelerated Cancer-Specific Host Death. Cell Rep. 2016 Oct.17(4):957-965. Pubmedid: 27760326. Pmcid: PMC5589518.
• Mosenson JA, Zloza A, Nieland JD, Garrett-Mayer E, Eby JM, Huelsmann EJ, Kumar P, Denman CJ, Lacek AT, Kohlhapp FJ, Alamiri A, Hughes T, Bines SD, Kaufman HL, Overbeck A, Mehrotra S, Hernandez C, Nishimura MI, Guevara-Patino JA, Le Poole IC. Mutant HSP70 reverses autoimmune depigmentation in vitiligo. Sci Transl Med. 2013 Feb.5(174):174ra28. Pubmedid: 23447019. Pmcid: PMC3912753.
• Diab A, Jenq RR, Rizzuto GA, Cohen AD, Huggins DW, Merghoub T, Engelhorn ME, Guevara-Patiño JA, Suh D, Hubbard-Lucey VM, Kochman AA, Chen S, Zhong H, Wolchok JD, van den Brink MR, Houghton AN, Perales MA. Enhanced responses to tumor immunization following total body irradiation are time-dependent. PLoS One. 2013 Dec.8(12):e82496. Pubmedid: 24349298. Pmcid: PMC3861406.
• Mosenson JA, Zloza A, Klarquist J, Barfuss AJ, Guevara-Patino JA, Poole IC. HSP70i is a critical component of the immune response leading to vitiligo. Pigment Cell Melanoma Res. 2012 Jan.25(1):88-98. Pubmedid: 21978301. Pmcid: PMC3662798.
• Zloza A, Kohlhapp FJ, Lyons GE, Schenkel JM, Moore TV, Lacek AT, O'Sullivan JA, Varanasi V, Williams JW, Jagoda MC, Bellavance EC, Marzo AL, Thomas PG, Zafirova B, Polić B, Al-Harthi L, Sperling AI, Guevara-Patiño JA. NKG2D signaling on CD8⁺ T cells represses T-bet and rescues CD4-unhelped CD8⁺ T cell memory recall but not effector responses. Nat Med. 2012 Feb.18(3):422-428. Pubmedid: 22366950. Pmcid: PMC3436127.
• Kohlhapp FJ, Zloza A, O'Sullivan JA, Moore TV, Lacek AT, Jagoda MC, McCracken J, Cole DJ, Guevara-Patiño JA. CD8(+) T cells sabotage their own memory potential through IFN-γ-dependent modification of the IL-12/IL-15 receptor α axis on dendritic cells. J Immunol. 2012 Apr.188(8):3639-3647. Pubmedid: 22430740. Pmcid: PMC3436124.
• O'Sullivan JA, Zloza A, Kohlhapp FJ, Moore TV, Lacek AT, Dulin NO, Guevara-Patiño JA. Priming with very low-affinity peptide ligands gives rise to CD8(+) T-cell effectors with enhanced function but with greater susceptibility to transforming growth factor (TGF)β-mediated suppression. Cancer Immunol Immun. 2011 Nov.60(11):1543-1551. Pubmedid: 21681376. Pmcid: PMC3327162.
• Orlandi F, Guevara-Patiño JA, Merghoub T, Wolchok JD, Houghton AN, Gregor PD. Combination of epitope-optimized DNA vaccination and passive infusion of monoclonal antibody against HER2/neu leads to breast tumor regression in mice. Vaccine. 2011 May.29(20):3646-3654. Pubmedid: 21435405.
• Bellavance EC, Kohlhapp FJ, Zloza A, O'Sullivan JA, McCracken J, Jagoda MC, Lacek AT, Posner MC, Guevara-Patino JA. Development of tumor-infiltrating CD8+ T cell memory precursor effector cells and antimelanoma memory responses are the result of vaccination and TGF-β blockade during the perioperative period of tumor resection. J Immunol. 2011 Mar.186(6):3309-3316. Pubmedid: 21289306. Pmcid: PMC3048906.
• Côté AL, Zhang P, O'Sullivan JA, Jacobs VL, Clemis CR, Sakaguchi S, Guevara-Patiño JA, Turk MJ. Stimulation of the glucocorticoid-induced TNF receptor family-related receptor on CD8 T cells induces protective and high-avidity T cell responses to tumor-specific antigens. J Immunol. 2011 Jan.186(1):275-283. Pubmedid: 21106849. Pmcid: PMC3050990.
• Zloza A, Jagoda MC, Lyons GE, Graves MC, Kohlhapp FJ, O'Sullivan JA, Lacek AT, Nishimura MI, Guevara-Patiño JA. CD8 co-receptor promotes susceptibility of CD8+ T cells to transforming growth factor-β (TGF-β)-mediated suppression. Cancer Immunol Immun. 2011 Feb.60(2):291-297. Pubmedid: 21193909. Pmcid: PMC4507403.
• Zloza A, Lyons GE, Chlewicki LK, Kohlhapp FJ, O'Sullivan JA, Lacek AT, Moore TV, Jagoda MC, Kumar V, Guevara-Patiño JA. Engagement of NK receptor NKG2D, but not 2B4, results in self-reactive CD8+ T cells and autoimmune vitiligo. Autoimmunity. 2011 Dec.44(8):599-606. Pubmedid: 21913803.
• Lazarou M, Guevara Patiño JA, Jennings RM, McIntosh RS, Shi J, Howell S, Cullen E, Jones T, Adame-Gallegos JR, Chappel JA, McBride JS, Blackman MJ, Holder AA, Pleass RJ. Inhibition of erythrocyte invasion and Plasmodium falciparum merozoite surface protein 1 processing by human immunoglobulin G1 (IgG1) and IgG3 antibodies. Infect Immun. 2009 Dec.77(12):5659-5667. Pubmedid: 19805526. Pmcid: PMC2786472.
• Denman CJ, McCracken J, Hariharan V, Klarquist J, Oyarbide-Valencia K, Guevara-Patiño JA, Le Poole IC. HSP70i accelerates depigmentation in a mouse model of autoimmune vitiligo. J Invest Dermatol. 2008 Aug.128(8):2041-2048. Pubmedid: 18337834. Pmcid: PMC3778919.
• Engelhorn ME, Guevara-Patiño JA, Merghoub T, Liu C, Ferrone CR, Rizzuto GA, Cymerman DH, Posnett DN, Houghton AN, Wolchok JD. Mechanisms of immunization against cancer using chimeric antigens. Mol Ther. 2008 Apr.16(4):773-781. Pubmedid: 18301399. Pmcid: PMC4399381.
• Houghton CS, Engelhorn ME, Liu C, Song D, Gregor P, Livingston PO, Orlandi F, Wolchok JD, McCracken J, Houghton AN, Guevara-Patiño JA. Immunological validation of the EpitOptimizer program for streamlined design of heteroclitic epitopes. Vaccine. 2007 Jul.25(29):5330-5342. Pubmedid: 17570567.
• Perales MA, Diab A, Cohen AD, Huggins DW, Guevara-Patiño JA, Hubbard VM, Engelhorn ME, Kochman AA, Eng JM, Mortazavi F, Alpdogan O, Terwey TH, Heller G, Wolchok JD, Houghton AN, van den Brink MR. DNA immunization against tissue-restricted antigens enhances tumor immunity after allogeneic hemopoietic stem cell transplantation. J Immunol. 2006 Sep.177(6):4159-4167. Pubmedid: 16951381.
• Guevara-Patiño JA, Engelhorn ME, Turk MJ, Liu C, Duan F, Rizzuto G, Cohen AD, Merghoub T, Wolchok JD, Houghton AN. Optimization of a self antigen for presentation of multiple epitopes in cancer immunity. J Clin Invest. 2006 May.116(5):1382-1390. Pubmedid: 16614758. Pmcid: PMC1435720.
• Engelhorn ME, Guevara-Patiño JA, Noffz G, Hooper AT, Lou O, Gold JS, Kappel BJ, Houghton AN. Autoimmunity and tumor immunity induced by immune responses to mutations in self. Nat Med. 2006 Feb.12(2):198-206. Pubmedid: 16444264.
• Goldberg SM, Bartido SM, Gardner JP, Guevara-Patiño JA, Montgomery SC, Perales MA, Maughan MF, Dempsey J, Donovan GP, Olson WC, Houghton AN, Wolchok JD. Comparison of two cancer vaccines targeting tyrosinase: plasmid DNA and recombinant alphavirus replicon particles. Clin Cancer Res. 2005 Nov.11(22):8114-8121. Pubmedid: 16299244.
• Palomba ML, Roberts WK, Dao T, Manukian G, Guevara-Patiño JA, Wolchok JD, Scheinberg DA, Houghton AN. CD8+ T-cell-dependent immunity following xenogeneic DNA immunization against CD20 in a tumor challenge model of B-cell lymphoma. Clin Cancer Res. 2005 Jan.11(1):370-379. Pubmedid: 15671568.
• Segal NH, Blachere NE, Guevara-Patiño JA, Gallardo HF, Shiu HY, Viale A, Antonescu CR, Wolchok JD, Houghton AN. Identification of cancer-testis genes expressed by melanoma and soft tissue sarcoma using bioinformatics. Cancer Immun. 2005 Feb.5:2. Pubmedid: 15683221.
• Turk MJ, Guevara-Patiño JA, Rizzuto GA, Engelhorn ME, Sakaguchi S, Houghton AN. Concomitant tumor immunity to a poorly immunogenic melanoma is prevented by regulatory T cells. J Exp Med. 2004 Sep.200(6):771-782. Pubmedid: 15381730. Pmcid: PMC2211964.
• Messaoudi I, Lemaoult J, Guevara-Patino JA, Metzner BM, Nikolich-Zugich J. Age-related CD8 T cell clonal expansions constrict CD8 T cell repertoire and have the potential to impair immune defense. J Exp Med. 2004 Nov.200(10):1347-1358. Pubmedid: 15545358. Pmcid: PMC2211915.
• Houghton AN, Guevara-Patiño JA. Immune recognition of self in immunity against cancer. J Clin Invest. 2004 Aug.114(4):468-471. Pubmedid: 15314682. Pmcid: PMC503781.
• Gregor PD, Wolchok JD, Ferrone CR, Buchinshky H, Guevara-Patiño JA, Perales MA, Mortazavi F, Bacich D, Heston W, Latouche JB, Sadelain M, Allison JP, Scher HI, Houghton AN. CTLA-4 blockade in combination with xenogeneic DNA vaccines enhances T-cell responses, tumor immunity and autoimmunity to self antigens in animal and cellular model systems. Vaccine. 2004 Apr.22(13-14):1700-1708. Pubmedid: 15068853.
• Ramirez-Montagut T, Turk MJ, Wolchok JD, Guevara-Patino JA, Houghton AN. Immunity to melanoma: unraveling the relation of tumor immunity and autoimmunity. Oncogene. 2003 May.22(20):3180-3187. Pubmedid: 12789294.
• Gold JS, Ferrone CR, Guevara-Patiño JA, Hawkins WG, Dyall R, Engelhorn ME, Wolchok JD, Lewis JJ, Houghton AN. A single heteroclitic epitope determines cancer immunity after xenogeneic DNA immunization against a tumor differentiation antigen. J Immunol. 2003 May.170(10):5188-5194. Pubmedid: 12734366.
• Guevara-Patiño JA, Turk MJ, Wolchok JD, Houghton AN. Immunity to cancer through immune recognition of altered self: studies with melanoma. Adv Cancer Res. 2003 Jan.90:157-177. Pubmedid: 14710950.
• Turk MJ, Wolchok JD, Guevara-Patino JA, Goldberg SM, Houghton AN. Multiple pathways to tumor immunity and concomitant autoimmunity. Immunol Rev. 2002 Oct.188:122-135. Pubmedid: 12445286.
• Messaoudi I, Guevara Patiño JA, Dyall R, LeMaoult J, Nikolich-Zugich J. Direct link between mhc polymorphism, T cell avidity, and diversity in immune defense. Science. 2002 Nov.298(5599):1797-1800. Pubmedid: 12459592.
• Uthaipibull C, Aufiero B, Syed SE, Hansen B, Guevara Patiño JA, Angov E, Ling IT, Fegeding K, Morgan WD, Ockenhouse C, Birdsall B, Feeney J, Lyon JA, Holder AA. Inhibitory and blocking monoclonal antibody epitopes on merozoite surface protein 1 of the malaria parasite Plasmodium falciparum. J Mol Biol. 2001 Apr.307(5):1381-1394. Pubmedid: 11292349.
• Guevara Patiño JA, Marino MW, Ivanov VN, Nikolich-Zugich J. Sex steroids induce apoptosis of CD8+CD4+ double-positive thymocytes via TNF-alpha. Eur J Immunol. 2000 Sep.30(9):2586-2592. Pubmedid: 11009092.
• Guevara Patiño JA, Ivanov VN, Lacy E, Elkon KB, Marino MW, Nikolic-Zugić J. TNF-alpha is the critical mediator of the cyclic AMP-induced apoptosis of CD8+4+ double-positive thymocytes. J Immunol. 2000 Feb.164(4):1689-1694. Pubmedid: 10657611.
• Kumar S, Collins W, Egan A, Yadava A, Garraud O, Blackman MJ, Guevara Patino JA, Diggs C, Kaslow DC. Immunogenicity and efficacy in aotus monkeys of four recombinant Plasmodium falciparum vaccines in multiple adjuvant formulations based on the 19-kilodalton C terminus of merozoite surface protein 1. Infect Immun. 2000 Apr.68(4):2215-2223. Pubmedid: 10722622. Pmcid: PMC97406.
• Holder AA, Guevara Patiño JA, Uthaipibull C, Syed SE, Ling IT, Scott-Finnigan T, Blackman MJ. Merozoite surface protein 1, immune evasion, and vaccines against asexual blood stage malaria. Parassitologia. 1999 Sep.41(1-3):409-414. Pubmedid: 10697894.
• Lacorazza HD, Guevara Patiño JA, Weksler ME, Radu D, Nikolić-Zugić J. Failure of rearranged TCR transgenes to prevent age-associated thymic involution. J Immunol. 1999 Oct.163(8):4262-4268. Pubmedid: 10510364.
• Guevara Patiño JA, Holder AA, McBride JS, Blackman MJ. Antibodies that inhibit malaria merozoite surface protein-1 processing and erythrocyte invasion are blocked by naturally acquired human antibodies. J Exp Med. 1997 Nov.186(10):1689-1699. Pubmedid: 9362529. Pmcid: PMC2199131.

• Title: CD3z-Independent Signaling Module for CAR-T Cell Therapies Against Solid Cancer
  Sponsor: Florida Biomedical Research Program (FBRP)
  PI: Guevara, J.
• Title: Comparative Analysis of a novel TRP1-NKG2D CAR-T Cells Versus 2nd Generation CARs in Melanoma
  Sponsor: Moffitt Cancer Center
  PI: Guevara, J.
• Title: Exploratory Study of T Cell Skin Trafficking and the Role of NKG2D Signaling; Implications in Vitiligo and Melanoma
  Sponsor: Nat Institutes of Health
  PI: Guevara, J.
• Title: Study of Anti-Tumor Immunity and Tissue Resident Memory Cell Development by NKG2D and Ribosomal Protein S6 Signaling in T cells
  Sponsor: Nat Institutes of Health
  PI: Guevara, J.