VISTA is an inhibitory immune checkpoint that is increased after ipilimumab therapy in patients with prostate cancer
Jianjun Gao, John F Ward, Curtis A Pettaway, Lewis Z Shi, Sumit K Subudhi, Luis M Vence, Hao Zhao, Jianfeng Chen, Hong Chen, Eleni Efstathiou, Patricia Troncoso, James P Allison, Christopher J Logothetis, Ignacio I Wistuba, Manuel A Sepulveda, Jingjing Sun, Jennifer Wargo, Jorge Blando, Padmanee Sharma, Jianjun Gao, John F Ward, Curtis A Pettaway, Lewis Z Shi, Sumit K Subudhi, Luis M Vence, Hao Zhao, Jianfeng Chen, Hong Chen, Eleni Efstathiou, Patricia Troncoso, James P Allison, Christopher J Logothetis, Ignacio I Wistuba, Manuel A Sepulveda, Jingjing Sun, Jennifer Wargo, Jorge Blando, Padmanee Sharma
Abstract
To date, anti-CTLA-4 (ipilimumab) or anti-PD-1 (nivolumab) monotherapy has not been demonstrated to be of substantial clinical benefit in patients with prostate cancer. To identify additional immune-inhibitory pathways in the prostate-tumor microenvironment, we evaluated untreated and ipilimumab-treated tumors from patients in a presurgical clinical trial. Levels of the PD-L1 and VISTA inhibitory molecules increased on independent subsets of macrophages in treated tumors. Our data suggest that VISTA represents another compensatory inhibitory pathway in prostate tumors after ipilimumab therapy.
Conflict of interest statement
COMPETING FINANCIAL INTERESTS
Drs. Sharma and Allison are founders and advisors for Jounce Therapeutics. Drs. Sharma and Allison are members of the Parker Institute for Cancer Immunotherapy. Dr. Sharma also serves as a consultant for BMS, AstraZeneca, Amgen and Glaxo SmithKline. Dr. Allison is an inventor of intellectual property owned by the University of California, Berkeley, and licensed to BMS and has received royalties from BMS. Dr. Allison is also inventor of intellectual property owned by Memorial-Sloan Kettering Cancer Center and licensed to Merck. Dr. Gao serves as a consultant for Genentech. Dr. Wistuba serves as a consultant for BMS. Dr. Efstathiou serves as a consultant for Janssen, Bayer, Medivation, Astellas and Sanofi Takeda.
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Source: PubMed