XCR1+ and CD11b+ migratory dendritic cells cooperate for the crosspriming of intratumoral CD8+ T cells with a tissue-resident memory phenotype [RNA-Seq]

The composition and diversity of tumor-infiltrating CD8+ T cell populations have important consequences on the development of anti-tumor immunity. In a murine model of lung cancer, we have addressed the role of dendritic cell subsets on the generation of various types of tumor-infiltrating CD8+ T cells. We show that CD44+PD1- effector and PD1+TIM3+ exhausted, tumor-infiltrating CD8+ T cells require XCR1+ DC1s but not IRF4-dependent CD11b+ DC2s. By contrast, CD103+CD69+ TRM-like, tumor-infiltrating CD8+ T cells require both DC1s and DC2s. The same requirement is found in tumor-draining lymph nodes where we identify CD103+ TRM-like precursors that are dependent on both XCR1+ DC1s and CD11b+, migratory DC2s. Mechanistically, we evidence that both types of migratory DCs cooperate. Mild TCR triggering by low MHCI-peptide density at the surface of cross-presenting migratory DC2s and low IL-12 support TGFb-dependent TRM specification in lymph nodes. High TCR triggering and high MHCI-peptide density at the surface of cross-presenting migratory DC1s and high IL-12 support proliferative expansion and CXCR6 acquisition. Altogether, these findings highlight the induction of intratumoral TRM-like cells under the collective aegis of multiple DCs subsets within tumor-draining lymph nodes reconciliating TRM phenotype instruction with proliferative expansion.