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.
Nature medicine. 2017 Mar 27 [Epub ahead of print]
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
Department of Genitourinary Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas, USA., Department of Urology, University of Texas MD Anderson Cancer Center, Houston, Texas, USA., The Immunotherapy Platform, University of Texas MD Anderson Cancer Center, Houston, Texas, USA., Department of Pathology, University of Texas MD Anderson Cancer Center, Houston, Texas, USA., Department of Translational Molecular Pathology, University of Texas MD Anderson Cancer Center, Houston, Texas, USA., Janssen Oncology Therapeutic Area, Janssen Research and Development, LLC, Pharmaceutical Companies of Johnson &Johnson, Spring House, Pennsylvania, USA., Department of Surgical Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas, USA.