Ms4a7 expression in cDC1s determines cross-presentation and antitumor immunity.

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 <i>Ms4a7</i>^-/- mice showed normal cDC1 development and turnover, they failed to prime antigen-specific CD8⁺ T cells following infection or tumor development. In human cancers, <i>MS4A7</i> 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.