The interplay of interleukin-17A and breast cancer tumor microenvironment as a novel immunotherapeutic approach to increase tumor immunogenicity

Abstract

Based on its known role in mediating tumor progression and the correlation with poor response to chemotherapy, we hypothesized that blocking interleukin-17A (IL-17A) by anti-IL-17 monoclonal antibodies might have the ability to suppress programmed death-ligand-1 (PD-L1) and to modulate the expression and function of myeloid-derived suppressor cells (MDSCs) in BC microenvironment. We also compared the apoptotic activity of anti-IL-17 with those acquired from our previous work on monoclonal antibodies against IL-6. The influence of anti-IL-17 was investigated in two doses on localized freshly resected tissues from 50 patients with BC. Results revealed increased IL-17A in BC tumor tissues versus surrounding tissues. Additionally, PD-L1 expression was inhibited in cultures treated with both doses of anti-IL-17. Frequencies of MDSCs were reduced in those cultures with anti-IL-17 with reduced suppressive activity. The induced apoptosis in the tumor cells was significantly increased. Anti-IL-17 antibodies effect was related to late stages, vascular metastasis, and hormonal status. Results of the current work suggest a promising role for anti-IL-17 monoclonal antibodies in enhancement of anti-tumor immunological activity in BC, potentially involving suppression of immune checkpoint PD-L1 and MDSCs inhibition with a marked response in aggressive disease.

Keywords: Anti-IL-17 monoclonal antibodies; Breast cancer; Interleukin-17A; Myeloid derived suppressor cells; Programmed death-ligand 1; T cell suppression; Tumor microenvironment.