The impact of aspirin on PD-L1 expression and alteration of M2 polarization in non-small cell lung cancer.

Abstract

Although aspirin is one of the best characterized drugs for the therapeutic effects on coagulation and inflammation, there are clues that it may also have a significant impact on cancer immunity. In this study, IFNg, a pro-inflammatory cytokine, has been demonstrated to increase the protein expression of PD-L1 in non-small cell lung carcinoma cells. In the molecular modeling of stimulated and/or aspirin-treated cancer secretome and macrophage interaction, CD38 (M1 macrophage marker) and CD209 (M2 macrophage marker) expressions confirmed that peripheral blood mononuclear cells differentiated into M1 or M2 macrophages afterwards polarization. Transcriptomic profiling was performed after 48 h of culture with differentiated M2-polarized macrophages in the presence of lung cancer cell secretomes. In contrast to the EGFR mutant aspirin-treated HCC827 cell line, the findings revealed that factors produced by the non-EGFR mutant aspirin-treated IFNg-induced H838 cancer cell secretome can alter M2 macrophage dynamics. Furthermore, significant patterns were obtained in gene expression profiles related to "Hematopoietic Cell Lineage" and "Antigen Processing and Presentation" between groups in M2-polarized macrophages established with these secretomes. However, aspirin treatment had different effects on cancer cell lines that expressed endogenous and induced PD-L1. As a result, flow cytometry analysis demonstrated that administering aspirin to HCC827 cancer cells boosted the expression of PD-L1 on their surface. Analysis of EGFR mutations, aspirin resistance, and PD-L1 levels, as well as M2 macrophage infiltration in the non-small cell lung cancer microenvironment and immune phenotyping of M2 macrophage subtypes, will assist in developing lung cancer therapy approaches that combine EGFR inhibitors and aspirin.