Platelets upregulate tumor cell programmed death ligand 1 in an epidermal growth factor receptor-dependent manner in vitro.

Guo, Q. ORCID: https://orcid.org/0000-0001-5332-4752, Malloy, M. W., Roweth, H. G. ORCID: https://orcid.org/0000-0002-1100-8409, McAllister, S. S., Italiano, J. E. and Battinelli, E. M. (2022) Platelets upregulate tumor cell programmed death ligand 1 in an epidermal growth factor receptor-dependent manner in vitro. Blood Advances, 6 (20). pp. 5668-5675. ISSN 2473-9529 doi: 10.1182/bloodadvances.2021006120

Abstract/Summary

Programmed death ligand 1 (PD-L1) is an immune checkpoint protein that suppresses cytotoxic T lymphocytes and is often overexpressed in cancers. Due to favorable clinical trial results, immune checkpoint inhibition (ICI) is part of Food and Drug Administration approved immuno-oncology therapies; however, not all patients benefit from ICI therapy. High blood platelet-to-lymphocyte ratio has been associated with failure of ICI treatment, but whether platelets have a role in hindering ICI response is unclear. Here, we report that coculturing platelets with cancer cell lines increased protein and gene expression of tumor cell PD-L1, which was reduced by antiplatelet agents, such as aspirin and ticagrelor. Platelet cytokine arrays revealed that the well-established cytokines, including interferon-γ, were not the main regulators of platelet-mediated PD-L1 upregulation. Instead, the high molecular weight epidermal growth factor (EGF) is abundant in platelets, which caused an upregulation of tumor cell PD-L1. Both an EGF-neutralizing antibody and cetuximab (EGF receptor [EGFR] monoclonal antibody) inhibited platelet-induced increases in tumor cell PD-L1, suggesting that platelets induce tumor cell PD-L1 in an EGFR-dependent manner. Our data reveal a novel mechanism for platelets in tumor immune escape and warrant further investigation to determine if targeting platelets improves ICI therapeutic responses.

Item Type	Article
URI	https://centaur.reading.ac.uk/id/eprint/127725
Identification Number/DOI	10.1182/bloodadvances.2021006120
Refereed	Yes
Divisions	No Reading authors. Back catalogue items Life Sciences > School of Biological Sciences > Biomedical Sciences
Publisher	American Society of Hematology
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