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PD-L1 on tumor cells is sufficient for immune evasion in immunogenic tumors and inhibits CD8 T cell cytotoxicity
- Source :
- The Journal of Experimental Medicine
- Publication Year :
- 2017
- Publisher :
- The Rockefeller University Press, 2017.
-
Abstract
- Both tumor- and host-derived PD-L1 can play critical roles in immunosuppression; differences in tumor immunogenicity appear to underlie their relative contributions. Juneja et al. show that in immunogenic MC38 tumors, PD-L1 on tumor cells dominates in suppressing tumor immunity by inhibiting CD8 T cell cytotoxicity.<br />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.
- Subjects :
- 0301 basic medicine
Cytotoxicity, Immunologic
Immunology
Programmed Cell Death 1 Receptor
chemical and pharmacologic phenomena
CD8-Positive T-Lymphocytes
Lymphocyte Activation
B7-H1 Antigen
03 medical and health sciences
Mice
0302 clinical medicine
Immune system
PD-L1
Cell Line, Tumor
medicine
Tumor Microenvironment
Immunology and Allergy
Cytotoxic T cell
Animals
Cytotoxicity
Melanoma
Research Articles
Tumor microenvironment
biology
Chemistry
Brief Definitive Report
medicine.disease
3. Good health
Mice, Inbred C57BL
030104 developmental biology
Tumor Escape
030220 oncology & carcinogenesis
biology.protein
Cancer research
Colorectal Neoplasms
CD8
Subjects
Details
- Language :
- English
- ISSN :
- 15409538 and 00221007
- Volume :
- 214
- Issue :
- 4
- Database :
- OpenAIRE
- Journal :
- The Journal of Experimental Medicine
- Accession number :
- edsair.doi.dedup.....e5b8a064d171bb973b432601e08c4357