Platelet PD-L1 suppresses anti-cancer immune cell activity in PD-L1 negative tumors

AB Zaslavsky, MP Adams, X Cao, T Maj, JE Choi… - Scientific Reports, 2020 - nature.com
AB Zaslavsky, MP Adams, X Cao, T Maj, JE Choi, J Stangl-Kremser, S Patel, A Putelo…
Scientific Reports, 2020nature.com
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 …
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.
nature.com
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