I am a Cancer Immunologist with a long-lasting interest in cancer immunotherapies, cancer vaccines and human T cell immunology. As an independent investigator, my research that focuses on immunotherapies of melanoma, T cell responses to melanoma antigens and on the mechanisms of melanoma-induced T cell dysfunction has been funded since 2002 by NIH/NCI RO1 grants as well as awards/contracts from the Cancer Research Institute, New-York and pharmaceutical industries. I have made seminal contributions in the field of human cancer immunology, identifying multiple novel tumor antigen-specific CD4 epitopes, and determining the role of the novel inhibitory receptor pathways Tim-3 and TIGIT in impeding T cell responses to melanoma. These findings have been translated into multiple first-in-human clinical trials in melanoma and other solid tumors, including cancer vaccines comprised of CD4 epitopes and adjuvants (CPG) and third generation immune checkpoint blockades with anti-Tim-3 or anti-TIGIT antibodies together with anti-PD-1 antibodies at HCC and other cancer centers in the US. Most recently, I have initiated translational studies evaluating the role of the gut microbiome in regulating clinical responses to PD-1 blockade in melanoma, including a first-in-human clinical trial to evaluate the safety and efficacy of fecal microbiota transplant (FMT) obtained from long-term PD-1 responder patients and pembrolizumab in PD-1 refractory melanoma patients. As a co-leader of the of the Cancer Immunology and Immunotherapy Program (CIIP), I will contribute to its mission, and together with basic and clinical investigators, foster the translation of novel laboratory findings into novel immunotherapy of cancers.
1. Chauvin JM, Pagliano O, Fourcade J, Sun Z, Hong Wang, Cindy Sanders, Kirkwood JM, Chen TT, Maurer M, Korman A.J, Zarour HM. TIGIT and PD-1 impair tumor antigen-specific CD8⁺ T cells in melanoma patients. J Clin Invest. 2015 May 125(5):2046-58. PMCID: PMC4463210.
2. Fourcade J, Sun Z, Pagliano O, Chauvin JM, Sander C, Janjic B, Tarhini AA, Tawbi HA, Kirkwood JM, Moschos S, Wang H, Guillaume P, Luescher IF, Krieg A, Anderson AC, Kuchroo VK, Zarour HM. PD-1 and Tim-3 regulate the expansion of tumor antigen-specific CD8⁺ T cells induced by melanoma vaccines. Cancer Res. 2014 15;74(4):1045-55. PMCID: PMC3952491.
3. Fourcade J, Sun Z, Benallaoua M, Guillaume P, Luescher IF, Sander C, Kirkwood JM, Kuchroo V, Zarour HM. Upregulation of Tim-3 and PD-1 expression is associated with tumor antigen-specific CD8⁺ T cell dysfunction in melanoma patients. J Exp Med. 2010 27;207(10):2175-86. PMCID: PMC2947081
4. Zarour HM, Kirkwood JM, Kierstead LS, Herr W, Brusic V, Singluff CL, Sidney J, Sette A and Storkus WJ. Melan-A/MART-1 (51-73) represents an immunogenic HLA-DR4-restricted epitope recognized by melanoma-reactive CD4(⁺) T cells. Proc Natl Acad Sci U S A, 2000, 4:97: 400-405 PMID: 10618430; PMCID: PMC26675