XCR1+ and CD11b+ migratory dendritic cells cooperate for the cross-priming of intratumoral CD8+ T cells with a tissue-resident memory phenotype.

XCR1+ and CD11b+ migratory dendritic cells cooperate for the cross-priming of intratumoral CD8+ T cells with a tissue-resident memory phenotype. | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Article XCR1 + and CD11b + migratory dendritic cells cooperate for the cross-priming of intratumoral CD8 + T cells with a tissue-resident memory phenotype. Pierre Guermonprez, Nathan Vaudiau, Pierre Bourdely, Agathe Ok, and 32 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6017264/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted You are reading this latest preprint version Abstract 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, immunotherapy responsive CD103+CXCR6+ 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+CXCR6+ 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 TGF-β -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. Biological sciences/Immunology/Tumour immunology Biological sciences/Immunology/Adaptive immunity Health sciences/Diseases/Cancer/Lung cancer/Non-small-cell lung cancer Biological sciences/Immunology/Antigen processing and presentation/Antigen-presenting cells Biological sciences/Immunology/Lymphocytes/T cells/CD8-positive T cells Full Text Additional Declarations There is NO Competing Interest. Cite Share Download PDF Status: Under Review Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-6017264","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":619833757,"identity":"2c07e708-5b32-4ee4-b053-0bd8adaaed25","order_by":0,"name":"Pierre 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