PD-L1 on tumor cells is sufficient for immune evasion in immunogenic tumors and inhibits CD8 T cell cytotoxicity
Brigham and Women's Hospital · Harvard University · +4 more institutions
Abstract
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…
Citation impact
- FWCI
- 32.73
- Percentile
- 100%
- References
- 37
Authors
8- VRVikram R. Juneja
Brigham and Women's Hospital, Harvard University, Harvard–MIT Division of Health Sciences and Technology
- KAKathleen A. McGuire
Brigham and Women's Hospital, Harvard University
- RTRobert T. Manguso
Harvard University, Dana-Farber Cancer Institute
- MWMartin W. LaFleur
Brigham and Women's Hospital, Harvard University, Dana-Farber Cancer Institute
- NBNatalie B. Collins
Broad Institute, Boston Children's Hospital, Harvard University, Dana-Farber Cancer Institute
Topics & keywords
- Cytotoxic T cell
- Cancer research
- Immune system
- Immunogenicity
- Melanoma
- Immunity
- Cytotoxicity
- Biology
- Good health and well-being