Faculty, Staff and Student Publications

Publication Date

5-19-2022

Journal

Cancers

Abstract

The interactions between platelets and cancer cells activate platelets and enhance tumor growth. Platelets increase proliferation and epithelial-mesenchymal transition in cancer cells, inhibit anoikis, enhance the extravasation of cancer cells, and protect circulating tumor cells against natural killer cells. Here, we have identified another mechanism by which platelets dampen the immune attack on cancer cells. We found that platelets can blunt the antitumor immune response by increasing the expression of inhibitory immune checkpoint (PD-L1) on ovarian cancer cells in vitro and in vivo. Platelets increased PD-L1 in cancer cells via contact-dependent (through NF-κB signaling) and contact-independent (through TFGβR1/Smad signaling) pathways. Inhibition of NF-κB or TGFβR1 signaling in ovarian cancer cells abrogated platelet-induced PD-L1 expression. Reducing platelet counts or inhibiting platelet functions reduced the expression of PD-L1 in ovarian cancer. On the other hand, an increase in platelet counts increased the expression of PD-L1 in tumor-bearing mice.

Keywords

NF-κB, PD-L1, TGFβR1, immunosuppression, ovarian cancer, platelet, tumor microenvironment

DOI

10.3390/cancers14102498

PMID

35626102

PMCID

PMC9139585

PubMedCentral® Posted Date

5-19-2022

PubMedCentral® Full Text Version

Post-print

Published Open-Access

yes

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