Peer-reviewedCC BY-NC-ND 4.0Nature Communications
Distinct migratory dendritic cell subsets cooperate to prime tissue-resident memory-like CD8⁺ T cells in mouse tumors
25 affiliations
- 1"Dendritic Cells and Adaptive Immunity" Unit, Immunology Department, Institut Pasteur, Paris, France.
- 2CNRS UMR3738 "Developmental Biology and Stem Cells", Institut Pasteur, Paris, France.
- 3Center for Vaccine and Immunotherapy, Institut Pasteur, Paris, France.
- 4INSERM UMR1149, CNRS EMR8252, Centre de Recherche sur l'Inflammation, Faculté de Médecine site Bichat, Université Paris Cité, Paris, France.
- 5Phagocytes and Cancer Immunology laboratory, INSERM U1016, CNRS UMR 8104, Institut Cochin, Université Paris Cité, Paris, France.
- 6Laboratory of Tumor Inflammation and Angiogenesis, Center for Cancer Biology, VIB, Leuven, Belgium.
- 7Laboratory of Tumor Inflammation and Angiogenesis, Center for Cancer Biology, Department of Oncology, KU Leuven, Leuven, Belgium.
- 8Roger Williams Institute of Liver Studies, School of Immunology & Microbial Sciences, Faculty of Life Sciences and Medicine, King's College London, Foundation for Liver Research and King's College Hospital, London, UK.
- 9Dynamics of Immune Responses Unit, INSERM U1223, Institut Pasteur, Université Paris Cité, Paris, France.
- 10U1356 Next Generation Immuno-Oncology Research, Gustave Roussy, Université Paris-Saclay, Villejuif, France.
- 11Singapore Immunology Network (SIgN), Agency for Science, Technology and Research, Singapore, Singapore.
- 12CNRS UMR9018 Cancer biology and metabolism, Gustave Roussy, Université Paris-Saclay, Villejuif, France.
- 13Center for Immunity and Inflammation, Rutgers New Jersey Medical School, Newark, NJ, USA.
- 14Department of Pathology, Immunology and Laboratory Medicine, Rutgers New Jersey Medical School, Newark, NJ, USA.
- 15Immunology-Immunopathology-Immunotherapy (i3), UMRS 959, INSERM, Sorbonne Université, Paris, France.
- 16Faculté de Médecine, Université Paris Cité, Paris, France.
- 17Nutrition and Obesity: Systemic Approaches, Inserm, Sorbonne University, Paris, France.
- 18Turing Center for Living Systems, Centre d'Immunologie de Marseille-Luminy, CNRS, INSERM, CIML, Aix-Marseille University, Marseille, France.
- 19INSERM U970, PARCC, Université de Paris Cité, Paris, France.
- 20Physiology and Cancer Research Programme, Champalimaud Research, Champalimaud Foundation, Lisbon, Portugal.
- 21Barts Cancer Institute, Queen Mary University of London, London, UK.
- 22International Centre for Genome Engineering and Biotechnology, Trieste, Italy.
- 23"Dendritic Cells and Adaptive Immunity" Unit, Immunology Department, Institut Pasteur, Paris, France. [email protected].
- 24CNRS UMR3738 "Developmental Biology and Stem Cells", Institut Pasteur, Paris, France. [email protected].
- 25Center for Vaccine and Immunotherapy, Institut Pasteur, Paris, France. [email protected].
Abstract
Tumor-infiltrating tissue-resident memory (TRM)-like CD8+ T cells correlate with positive prognosis and better responses to cancer immunotherapy, yet the mechanisms underlying their specification remain ill-understood. Here, we use the KP (KrasG12D, p53-/-) mouse model of lung adenocarcinoma to investigate how different dendritic cell (DC) subsets shape tumor-specific CD8+ T cell responses. Selective ablation of XCR1+ DC1s or IRF4-dependent CD11b+ DC2s reveal that DC1s, but not DC2s, are required for the generation of tumor-infiltrating effector and exhausted CD8+ T cells. By contrast, both migratory DC1s and migratory DC2s contribute to the specification of CD103+CD69+ TRM-like CD8+ T cells in tumor-draining lymph nodes. Mechanistically, low peptide/MHC-I density on migratory DC2s favors TGFβ-dependent TRM differentiation, while high peptide/MHC-I density on DC1s promote proliferative expansion of TRM-like cells; in addition, IL-12 secreted by DC1s enhances CXCR6 expression. Together, our findings uncover complementary functions of migratory DC subsets in shaping anti-tumor TRM-like CD8+ T cell responses, and also implicate targeting multiple DC subsets for optimizing cancer immunotherapy.
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BibTeX
@article{vaudiau2026distinct,
title = {{Distinct migratory dendritic cell subsets cooperate to prime tissue-resident memory-like CD8⁺ T cells in mouse tumors}},
author = {Nathan Vaudiau and Pierre Bourdely and Maria Semitekolou and Agathe Ok and Louise Gorline and Aboubacar Sidiki K Coulibaly and Matthieu Rastello and Aurélie Semervil and Roberto Savoldelli and Yohan Gerber-Ferder and Fillipe Luiz Rosa do Carmo and Mathias Vétillard and Audrey Rood and Jérémie Bornères and Abdenour Abbas and Marie Guillin and Judith Weber and Syrine Bouallegue and Konstantina Pamboukas and Zacarias Garcia and Florent Ginhoux and Camille Blériot and Philippe Bousso and Yosuke Kumamoto and Guillaume Darrasse-Jèze and Emmanuel L Gautier and Marc Dalod and Eric Tartour and Tessa Bergsbaken and Klaas P J M Van Gisbergen and Kairbaan M Hodivala-Dilke and Massimiliano Mazzone and Loredana Saveanu and Julie Helft and Federica Benvenuti and Pierre Guermonprez},
journal = {Nature Communications},
year = {2026},
month = sep,
doi = {10.1038/s41467-026-77641-7},
url = {https://hal.science/hal-05762918v1},
note = {CC BY-NC-ND 4.0},
}
RIS
TY - JOUR
TI - Distinct migratory dendritic cell subsets cooperate to prime tissue-resident memory-like CD8⁺ T cells in mouse tumors
AU - Nathan Vaudiau
AU - Pierre Bourdely
AU - Maria Semitekolou
AU - Agathe Ok
AU - Louise Gorline
AU - Aboubacar Sidiki K Coulibaly
AU - Matthieu Rastello
AU - Aurélie Semervil
AU - Roberto Savoldelli
AU - Yohan Gerber-Ferder
AU - Fillipe Luiz Rosa do Carmo
AU - Mathias Vétillard
AU - Audrey Rood
AU - Jérémie Bornères
AU - Abdenour Abbas
AU - Marie Guillin
AU - Judith Weber
AU - Syrine Bouallegue
AU - Konstantina Pamboukas
AU - Zacarias Garcia
AU - Florent Ginhoux
AU - Camille Blériot
AU - Philippe Bousso
AU - Yosuke Kumamoto
AU - Guillaume Darrasse-Jèze
AU - Emmanuel L Gautier
AU - Marc Dalod
AU - Eric Tartour
AU - Tessa Bergsbaken
AU - Klaas P J M Van Gisbergen
AU - Kairbaan M Hodivala-Dilke
AU - Massimiliano Mazzone
AU - Loredana Saveanu
AU - Julie Helft
AU - Federica Benvenuti
AU - Pierre Guermonprez
PY - 2026
DA - 2026/09/18
JO - Nature Communications
DO - 10.1038/s41467-026-77641-7
UR - https://hal.science/hal-05762918v1
AB - Tumor-infiltrating tissue-resident memory (TRM)-like CD8+ T cells correlate with positive prognosis and better responses to cancer immunotherapy, yet the mechanisms underlying their specification remain ill-understood. Here, we use the KP (KrasG12D, p53-/-) mouse model of lung adenocarcinoma to investigate how different dendritic cell (DC) subsets shape tumor-specific CD8+ T cell responses. Selective ablation of XCR1+ DC1s or IRF4-dependent CD11b+ DC2s reveal that DC1s, but not DC2s, are required for the generation of tumor-infiltrating effector and exhausted CD8+ T cells. By contrast, both migratory DC1s and migratory DC2s contribute to the specification of CD103+CD69+ TRM-like CD8+ T cells in tumor-draining lymph nodes. Mechanistically, low peptide/MHC-I density on migratory DC2s favors TGFβ-dependent TRM differentiation, while high peptide/MHC-I density on DC1s promote proliferative expansion of TRM-like cells; in addition, IL-12 secreted by DC1s enhances CXCR6 expression. Together, our findings uncover complementary functions of migratory DC subsets in shaping anti-tumor TRM-like CD8+ T cell responses, and also implicate targeting multiple DC subsets for optimizing cancer immunotherapy.
SN - 2041-1723
SN - 2041-1723
ER -