TY - JOUR AB - 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 subsets and PD‑L1 expression was reversed after further transfection of THP‑1 cells with HIF‑1α siRNA (P<0.05). After co‑culturing, T‑cell proliferation was inhibited and apoptosis was promoted. In summary, modulation of lactic acid level can redistribute M2‑TAM subsets and upregulate PD‑L1 to assist tumor immune escape. The HIF‑1α signaling pathway may participate in this process, revealing that macrophages, as ‘checkpoints’ in organisms, are links that connect the immune status and tumor evolution, and can be used as a target in tumor treatment. AD - Department of General Surgery, The Second Affiliated Hospital of Medical College, Xi'an Jiaotong University, Xi'an, Shaanxi 710004, P.R. China Department of Chemistry, School of Science, Xi'an Jiaotong University, Xi'an, Shaanxi 710004, P.R. China Department of Pathology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA Department for Population and Development Studies, School of Public Policy and Administration, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China Department of General Surgery, First Affiliated Hospital of Medical College, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China Department of Surgical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA AU - Shan,Tao AU - Chen,Shuo AU - Chen,Xi AU - Wu,Tao AU - Yang,Yi AU - Li,Shunle AU - Ma,Jiancang AU - Zhao,Jing AU - Lin,Wanrun AU - Li,Wei AU - Cui,Xijuan AU - Kang,Ya'an DA - 2020/11/01 DO - 10.3892/or.2020.7767 EP - 1894 IS - 5 JO - Oncol Rep KW - microenvironment pancreatic cancer lactic acid TAM HIF‑1α PD‑L1 PY - 2020 SN - 1021-335X 1791-2431 SP - 1885 ST - M2‑TAM subsets altered by lactic acid promote T‑cell apoptosis through the PD‑L1/PD‑1 pathway T2 - Oncology Reports TI - M2‑TAM subsets altered by lactic acid promote T‑cell apoptosis through the PD‑L1/PD‑1 pathway UR - https://doi.org/10.3892/or.2020.7767 VL - 44 ER -