PD-L1 on tumor cells is sufficient for immune evasion in immunogenic tumors and inhibits CD8 T cell cytotoxicity

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...

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Vydáno v:The Journal of experimental medicine Ročník 214; číslo 4; s. 895 - 904
Hlavní autoři: Juneja, Vikram R, McGuire, Kathleen A, Manguso, Robert T, LaFleur, Martin W, Collins, Natalie, Haining, W Nicholas, Freeman, Gordon J, Sharpe, Arlene H
Médium: Journal Article
Jazyk:angličtina
Vydáno: United States 03.04.2017
Témata:
Animals
B7-H1 Antigen - physiology
CD8-Positive T-Lymphocytes - immunology
Cell Line, Tumor
Colorectal Neoplasms - immunology
Cytotoxicity, Immunologic
Lymphocyte Activation
Melanoma - immunology
Mice
Mice, Inbred C57BL
Programmed Cell Death 1 Receptor - physiology
Tumor Escape
Tumor Microenvironment
ISSN:1540-9538
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Shrnutí: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.
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ISSN:1540-9538
DOI:10.1084/jem.20160801