Ms4a7 expression in cDC1s determines cross-presentation and anti-tumor immunity

Type 1 conventional 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 for activating CD8+ T cell immunity are not well understood. Here, we found that Ms4a7 was selectively expressed in cDC1s after engulfing tumor antigens or exposed to exogenous antigens, and required for their cross-priming ability and migration to dLNs. Ms4a7-/- mice showed normal cDC1 development and turnover but failed to prime antigen-specific CD8+ T cells after infection or tumor development. In human cancers, MS4A7 specifically expressed in a subset of cDC1s which preferentially enriched in dLNs, playing a crucial role in patient survival. Our findings reveal a critical role of Ms4a7 in cDC1 migration, cross-presentation and anti-tumor CD8+ T cell responses. Overall design: For in vitro samle: Flt3L-induced DCs (Day 9) were sorted as live B220-MHC II(high)CD11c(high)CD24+CD172a- (cDC1) and live B220-MHC II(high)CD11c(high)CD24-CD172a+ (cDC2). After treatment with or without LPS (100 ng/ml), cells were collected for RNA-seq and ATAC-seq. For in vivo sample: Tumors grown for 18 days were harvested and cDCs or other antigen presenting cells loaded with (GFP+) or without (GFP-) within TME and dLNs were sorted as as live CD45+TCRß-MHC IIhighCD11high GFP+ (GFP+ cDCs), CD45+TCRß-MHC IIhighCD11high GFP- (GFP- cDCs), CD45+TCRß-MHC II+CD11c-GFP+ (GFP+ nAPCs, non-cDC APCs) and CD45+TCRß-MHC II+CD11c-GFP- (GFP- nAPCs).