%0 Journal Article %J J Exp Med %D 2017 %T PD-L1 on tumor cells is sufficient for immune evasion in immunogenic tumors and inhibits CD8 T cell cytotoxicity %A Juneja, Vikram R %A McGuire, Kathleen A %A Manguso, Robert T %A LaFleur, Martin W %A Collins, Natalie %A Haining, W Nicholas %A Freeman, Gordon J %A Sharpe, Arlene H %X

It 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.

PubMed DOI

%B J Exp Med %V 214 %P 895-904 %8 2017 Apr 03 %G eng %N 4 %1 http://www.ncbi.nlm.nih.gov/pubmed/28302645?dopt=Abstract %R 10.1084/jem.20160801