Endoplasmic Reticulum Stress Promotes Prostate Cancer Cells to Release Exosome and Up-regulate PD-L1 Expression via PI3K/Akt Signaling Pathway in Macrophages

Abstract

Mounting evidence has demonstrated that endoplasmic reticulum stress (ERS) serves an important role in shaping the immunosuppressive microenvironment by modulating resident tumor-associated macrophages (TAMs). However, the communication between ER‑stressed tumor cells and TAMs is not fully understood. Exosomes have been reported to play a vital role in intercellular communication. Therefore, in order to investigate the role of ER stress‑related exosomes in prostate cancer cells promoting macrophage infiltration and polarization, laser scanning confocal microscope, RT-PCR, flow cytometric analysis, western‑blotting and cytokine bead array analyses were performed.The results demonstrated that TG-EXO downregulated the expression of PD-L1 on macrophages through flow cytometry analysis. In addition, Compared with CON-EXO, the expression of macrophage-associated inflammatory cytokines IL-12, TNF-α and IL-1βwas significantly decreased in TG-EXO treatment (P< 0.05). TG-EXO upregulated the expression levels of IL-6, IL-10 and TGF-β cytokinesin macrophages. Our research shows that TG-EXO increased PI3K/AKT signaling pathway compared to the CON-EXO group. In summary, we found exosomes from TG-treated prostate cancer cells altered the immunosupression status and affected macrophages polarization by up-regulating the expression of PD-L1 and inflammatory factors and PI3K/AKT pathway.