M2 ‑TAM subsets altered by lactic acid promote T‑cell apoptosis through the PD‑L1/PD‑1 pathway.

M2‑TAM subsets altered by lactic acid promote T‑cell apoptosis through the PD‑L1/PD‑1 pathway. Oncol Rep. 2020 Nov;44(5):1885-1894 Authors: Shan T, Chen S, Chen X, Wu T, Yang Y, Li S, Ma J, Zhao J, Lin W, Li W, Cui X, Kang Y Abstract The aim of the study was to investigate the effects of lactic acid on the phenotypic polarization and immune function of macrophages. The human monocyte/macrophage cell line, THP‑1, was selected and treated with lactic acid. Immunofluorescence staining, laser confocal microscopy, reverse‑transcription polymerase chain reaction (RT‑PCR), western blot, siRNA, and ELISA analyses were used to observe changes in the levels of cluster of differentiation (CD)68, CD163, hypoxia inducible factor (HIF)‑1α, and programmed death ligand‑1 (PD‑L1) as well as those of cytokines, tumor necrosis factor (TNF)‑α, interferon (IFN)‑γ, interleukin (IL)‑12, and IL‑10. THP‑1 macrophages and T cells were co‑cultured in vitro to observe the changes in proliferation and apoptosis of T cells. The results showed that, lactic acid (15 mmol/l) significantly upregulated the expression of the macrophage M2 marker CD163 (P<0.05), cytokines, IFN‑γ and IL‑10, secreted by M2‑tumor‑associated macrophages (TAM, P<0.05), and HIF‑1α and PD‑L1 (P<0.05), and downregulated the expression of cytokines, TNF‑α and IL‑12, secreted by M1‑TAM (P<0.05). Redistribution of M2‑TAM subse...
Source: Oncology Reports - Category: Cancer & Oncology Tags: Oncol Rep Source Type: research