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

GSE255477 Mus musculus Expression profiling by high throughput sequencing; Genome binding/occupancy profiling by high throughput sequencing 40 samples 2025/11/30 GPL24247
Summary
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.
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