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

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