LRCH1 deficiency enhances LAT signalosome formation and CD8 <sup>+</sup> T cell responses against tumors and pathogens
Chang Liu, Xiaoyan Xu, Lei Han, Xiaopeng Wan, Lingming Zheng, Chunyang Li, Zhaohui Liao, Jun Xiao, Ruiyue Zhong, Xin Zheng, Qiong Wang, Zonghai Li, Hualan Chen, Bin Wei, Hongyan Wang
Abstract
Significance Improving cytotoxicity, proliferation, and infiltration ability of CD8 + T cells is critical in T cell immunotherapies against tumors. This study has identified LRCH1 as a negative regulator of LAT-mediated TCR signal transduction, as LRCH1 inhibits LAT signalosome formation and facilitates the endocytosis of LAT on the plasma membrane. LRCH1-deficient CD8 + T cells are more proliferative and effective at pathogen control and tumor elimination. Importantly, CRISPR-Cas9–mediated knockout of LRCH1 in human T cells also increases IFN-γ production, cell proliferation, and migration ability in vitro. These data suggest LRCH1 as a potential target to improve CD8 + T cell responses against tumors and pathogens.