Cross-presentation of dead cell-associated antigens shapes the neoantigenic landscape of tumour immunity

Anti-tumour effector CD8+ T cells are often specific 1 for neoantigens that arise from mutations 2 in cancer cells. These effectors are often primed by type 1 conventional dendritic cells (cDC1s) 3 that cross-present cancer neoantigens on MHC class I molecules. However, the process of 4 tumour antigen acquisition and cross-presentation (XP) by cDC1 remains poorly understood 5 and whether it selects for certain types of cancer neoantigens has not been addressed. In 6 both mice and humans, cDC1s are marked by high expression of DNGR-1 (a.k.a. CLEC9A), 7 a receptor that binds to F-actin exposed by cell debris and signals to favour XP of dead cell8 associated antigens. Here we demonstrate a role for DNGR-1-dependent XP in determining 9 tumour immunogenicity during cancer development in mice. We show that mice lacking 10 DNGR-1 display shorter latency for chemically-induced tumourigenesis compared to 11 immunocompetent wild-type (WT) hosts