Prostat Kanserinde Tlr Agonistlerinin M1, M2 Makrofaj Polarizasyonunda Rolü

Abstract

It is well known that inflammation is effective in the development of prostate cancer. Macrophages in the tumor microenvironment are either anti-inflammatory M2-type that help tumor growth or pro-inflammatory M1-type that play an important role in the recognition and destruction of cancer cells. Inflammatory cytokines such as IL-10, TGFβ, IL-6 and IL-8 that are produced from TAMs in the tumor microenvironment facilitate the development and metastasis of cancer cells. The higher number of TAMs is commonly obsereved in tumors with poor prognosis. Therefore, control and regulation of TAMs play a key role in the prognosis of tumors. Various Toll Like Receptor (TLR) agonists are used in clinical applications because they can direct the immune response against the tumor. Soluble factors released from the tumor are known to be effective in transformation to TAMs. However, the effects of soluble factors released from prostate cancer cells on macrophage polarization are not well known. Therefore, in our study, the effects of factors released from prostate cancer cells which were treated with TLR 4 and TLR 8 agonists on the differentiation of macrophages were investigated. In addition, phagocytosis functions of macrophages as well as cytokines released from macrophages were evaluated. We found that THP1 cells showed decreased expression of CD206 in the presence of the supernatant from PC3 cells treated with TLR4 and TLR8 agonists. In these cells, the inflammatory cytokines IL-1α, IL-1β, TNFα, IFNγ and GM-CSF were increased. In these conditions, the phagocytosis capacity increased in the THP-1 cells and the cell cycle of these cells showed the G0 / G1 phase.