ATM-AMPK α mediated LAG-3 expression suppresses T cell function in prostate cancer

Cell Immunol. 2023 Sep 28;393-394:104773. doi: 10.1016/j.cellimm.2023.104773. Online ahead of print.ABSTRACTImmunotherapy for prostate cancer (PCa) faces serious challenges. Therefore, the co-inhibitory receptors that regulate T cell function of PCa must be elucidated. Here we identified that the inhibitory receptor LAG3 was significantly induced in T cells from PCa patients. Gene array analysis revealed that insufficient ataxia telangiectasia mutated (ATM) gene expression in PCa T cells was responsible for the elevated LAG3 expression. Mechanistically, insufficient ATM expression impaired its ability to activate AMPKα signaling and CD4+ T cell functions, which further enhances the binding of the transcription factors XBP1 and EGR2 to LAG3 promoter. Reconstitution of ATM and inhibition of XBP1 or EGR2 in PCa T cells suppressed LAG3 expression and restored the effector function of CD4+ T cells from PCa. Our study revealed the mechanism of LAG3 upregulation in CD4+ T lymphocytes of PCa patients and may provide insights for the development of immunotherapeutic strategies for PCa treatment.PMID:37857190 | DOI:10.1016/j.cellimm.2023.104773

Source: Cellular Immunology - October 19, 2023 Category: Allergy & Immunology Authors: Xinyao Zhang Haiqi Chen Jiawen Han Zongren Wang Yu Guo Zhongyang Zhou Rong Luo Meiqin Dai Wei Ou Lingwu Chen Lan Shao Source Type: research