Juneja, Vikram R.McGuire, Kathleen A.Manguso, Robert T.LaFleur, MartinCollins, NatalieHaining, W. NicholasFreeman, Gordon J.Sharpe, Arlene2017-12-062017Juneja, Vikram R., Kathleen A. McGuire, Robert T. Manguso, Martin W. LaFleur, Natalie Collins, W. Nicholas Haining, Gordon J. Freeman, and Arlene H. Sharpe. 2017. “PD-L1 on tumor cells is sufficient for immune evasion in immunogenic tumors and inhibits CD8 T cell cytotoxicity.” The Journal of Experimental Medicine 214 (4): 895-904. doi:10.1084/jem.20160801. http://dx.doi.org/10.1084/jem.20160801.http://nrs.harvard.edu/urn-3:HUL.InstRepos:34492460It is unclear whether PD-L1 on tumor cells is sufficient for tumor immune evasion or simply correlates with an inflamed tumor microenvironment. We used three mouse tumor models sensitive to PD-1 blockade to evaluate the significance of PD-L1 on tumor versus nontumor cells. PD-L1 on nontumor cells is critical for inhibiting antitumor immunity in B16 melanoma and a genetically engineered melanoma. In contrast, PD-L1 on MC38 colorectal adenocarcinoma cells is sufficient to suppress antitumor immunity, as deletion of PD-L1 on highly immunogenic MC38 tumor cells allows effective antitumor immunity. MC38-derived PD-L1 potently inhibited CD8+ T cell cytotoxicity. Wild-type MC38 cells outcompeted PD-L1–deleted MC38 cells in vivo, demonstrating tumor PD-L1 confers a selective advantage. Thus, both tumor- and host-derived PD-L1 can play critical roles in immunosuppression. Differences in tumor immunogenicity appear to underlie their relative importance. Our findings establish reduced cytotoxicity as a key mechanism by which tumor PD-L1 suppresses antitumor immunity and demonstrate that tumor PD-L1 is not just a marker of suppressed antitumor immunity.en-USBrief Definitive ReportJournal Article2017-12-0610.1084/jem.20160801