Ms4a7 expression in cDC1s determines cross-presentation and antitumor immunity
Bowen Xie, Bowen Yuan, Xiaohong Zhao, Tian Xie, Ruifeng Li, Peng Wei, Qinli Sun, Wenbo Hu, Birui Pan, Yongzhen Chen, Kun Wei, Zixuan Zhao, Lei Yuan, Xuan Zhong, Xue Bai, Qiuyan Lan, Lei Qin, Ling Ni, Chen Dong
Abstract
Conventional type 1 dendritic cells (cDC1s) capture antigens in peripheral tissues and migrate to draining lymph nodes (dLNs) to prime antigen-specific CD8 + T cells. How tumor antigens are processed to activate CD8 + T cell immunity is not well understood. In this work, we show that Ms4a7 is up-regulated in cDC1s after tumor antigen uptake or exposure to exogenous stimuli and is required for their cross-priming ability. Although Ms4a7 −/− mice showed normal cDC1 development and turnover, they failed to prime antigen-specific CD8 + T cells following infection or tumor development. In human cancers, MS4A7 was expressed in a subset of cDC1s, preferentially enriched in dLNs, and correlated with patient survival. Our findings suggest a critical role for Ms4a7 in cDC1-mediated cross-presentation and antitumor CD8 + T cell responses.