Publication: XCR1+ and IRF4+ migratory dendritic cells cooperate for the cross-priming of intratumoral CD8+ T cells with a tissue-resident memory phenotype

Published in:

Authors: Nathan Vaudiau, Pierre Bourdely, Agathe Ok, Maria Semitekolou, Louise Gorline, Roberto Savoldelli, Yohan Gerber-Ferder, Fillipe Luiz Rosa Do Carmo, Aurélie Semervil, Mathias Vétillard, Audrey Rood, Syrine Bouallègue, Konstantina Pamboukas, Jérémie Borneres, Guillaume Darasse-Jèze, Emmanuel Gautier, Marc Dalod, Eric Tartour, Tessa Bergsbaken, Klaas Gisbergen, Kairbaan Hodivala-Dilke, Loredana Saveanu, Julie Helft, Federica Benvenuti, Pierre Guermonprez

Summary

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 + DCs but not IRF4-dependent DCs. By contrast, CD103 + CXCR6 + T RM -like, tumor-infiltrating CD8 + T cells require both XCR1 + DCs and IRF4-dependent DCs. The same requirement is found in tumor-draining lymph nodes where we identify CD103 + CXCR6 + T RM -like precursors that are dependent on both XCR1 + DCs and IRF4-dependent migratory DCs. 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 T RM 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 T RM -like cells under the collective aegis of multiple DCs subsets within tumor-draining lymph nodes reconciliating T RM phenotype instruction with proliferative expansion.

Link to HAL – hal-05407318

Link to DOI – 10.21203/rs.3.rs-6455825/v1