학술논문

Platelet PD-L1 suppresses anti-cancer immune cell activity in PD-L1 negative tumors.
Document Type
Article
Source
Scientific Reports. 11/9/2020, Vol. 10 Issue 1, pN.PAG-N.PAG. 1p.
Subject
*APOPTOSIS
*PROGRAMMED death-ligand 1
*PLATELET-derived growth factor
*CANCER cells
*TUMOR microenvironment
*PLATELET aggregation inhibitors
Language
ISSN
2045-2322
Abstract
Strategies that interfere with the binding of the receptor programmed cell death protein-1 (PD-1) to programmed death ligand-1 (PD-L1) have shown marked efficacy against many advanced cancers, including those that are negative for PD-L1. Precisely why patients with PD-L1 negative tumors respond to PD-1/PD-L1 checkpoint inhibition remains unclear. Here, we show that platelet-derived PD-L1 regulates the growth of PD-L1 negative tumors and that interference with platelet binding to PD-L1 negative cancer cells promotes T cell-induced cancer cytotoxicity. These results suggest that the successful outcomes of PD-L1 based therapies in patients with PD-L1 negative tumors may be explained, in part, by the presence of intra-tumoral platelets. Altogether, our findings demonstrate the impact of non-cancer/non-immune cell sources of PD-L1 in the tumor microenvironment in the promotion of cancer cell immune evasion. Our study also provides a compelling rationale for future testing of PD-L1 checkpoint inhibitor therapies in combination with antiplatelet agents, in patients with PD-L1 negative tumors. [ABSTRACT FROM AUTHOR]