1. Department of Urology, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, PR China
2. Institute of Urology, Anhui Medical University, Hefei, Anhui, PR China
3. Department of Blood Transfusion, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, PR China
4. Department of Clinical Laboratory, The Affiliated Chaohu Hospital of Anhui Medical University, ChaoHu, Anhui, PR China
#Authors contributed equally
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.
Keywords: Exosomes, Endoplasmic reticulum stressed, Prostate cancer cells, PI3K/Akt, Macrophages