Peer-reviewedCC BYImmunity
CCR7+ activated dendritic cells are essential for spontaneous and immunotherapy-driven anti-tumor immunity
9 affiliations
- 1Cancer Inflammation and Immunity, Cancer Research UK Manchester Institute, The University of Manchester, Manchester, UK
- 2Computational Biology Support, Cancer Research UK Manchester Institute, The University of Manchester, Manchester, UK
- 3Flow Cytometry, Cancer Research UK Manchester Institute, The University of Manchester, Manchester, UK
- 4Cancer Inflammation and Immunity, Cancer Research UK Manchester Institute, The University of Manchester, Manchester, UK; Dermatology Centre, Northern Care Alliance NHS Foundation Trust & Division of Musculoskeletal and Dermatological Sciences, Manchester NIHR Biomedical Research Centre, Manchester Academic Health Science Centre, The University of Manchester, Manchester, UK
- 5Centre d'Etude des Pathologies Respiratoires, INSERM, UMR 1100, Université de Tours, Tours, France
- 6Centre d'Immunologie de Marseille-Luminy, INSERM, CNRS, Aix Marseille Université, Marseille, France; Centre d'Immunophénomique, INSERM, CNRS, PHENOMIN, Celphedia, Aix Marseille Université, Marseille, France
- 7Lydia Becker Institute of Immunology and Inflammation, The University of Manchester, Manchester, UK
- 8Genome Editing and Mouse Models, Cancer Research UK Manchester Institute, The University of Manchester, Manchester, UK
- 9Cancer Inflammation and Immunity, Cancer Research UK Manchester Institute, The University of Manchester, Manchester, UK; Lydia Becker Institute of Immunology and Inflammation, The University of Manchester, Manchester, UK. Electronic address: [email protected]
Abstract
Single-cell transcriptomics identifies a convergent activation state of conventional dendritic cells (cDCs) shared by type 1 and type 2 cDCs (cDC1s and cDC2s). These activated DCs (actDCs) are characterized by co-expression of T cell-stimulating and inhibitory molecules. Here, we examined the functional contribution of actDCs to anti-tumor immunity by developing mouse models that leverage CCR7 expression to conditionally label or ablate actDCs. The capacity of cDCs to stimulate tumor-specific cytotoxic T lymphocytes (CTLs) was restricted to the actDC state. cDC1- and cDC2-derived actDCs supported CTL priming through cross-presentation and cross-dressing, respectively, with the latter occurring in a cancer type-dependent manner. actDCs were required for the activation of naive CTLs in tumor-draining lymph nodes and for sustaining effector CTL function within tumors. Consequently, ablation of actDCs impaired spontaneous tumor control and responses to immune checkpoint blockade or adoptive T cell therapy. Thus, the actDC state emerges as a critical determinant of cDC-mediated anti-tumor immunity.
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BibTeX
@article{koufaki2026ccr7,
title = {{CCR7+ activated dendritic cells are essential for spontaneous and immunotherapy-driven anti-tumor immunity}},
author = {Maria A. Koufaki and Erin Richardson and Eduardo Bonavita and Richard Reeves and Agrin Moeini and Shih‐Chieh Chiang and Antonia Banyard and Massimo Russo and Charles H. Earnshaw and Charlotte R. Bell and Eimear Flanagan and Victoria S. Pelly and Laëtitia Nebot-Bral and Anna Pidoux and Poppy Dunn and Sudhakar Sahoo and Sandrine Henri and Bernard MALISSEN and Andrew S. MacDonald and Natalia Moncaut and Santiago Zelenay},
journal = {Immunity},
year = {2026},
month = aug,
doi = {10.1016/j.immuni.2026.07.002},
url = {https://doi.org/10.1016/j.immuni.2026.07.002},
note = {CC BY},
}
RIS
TY - JOUR
TI - CCR7+ activated dendritic cells are essential for spontaneous and immunotherapy-driven anti-tumor immunity
AU - Maria A. Koufaki
AU - Erin Richardson
AU - Eduardo Bonavita
AU - Richard Reeves
AU - Agrin Moeini
AU - Shih‐Chieh Chiang
AU - Antonia Banyard
AU - Massimo Russo
AU - Charles H. Earnshaw
AU - Charlotte R. Bell
AU - Eimear Flanagan
AU - Victoria S. Pelly
AU - Laëtitia Nebot-Bral
AU - Anna Pidoux
AU - Poppy Dunn
AU - Sudhakar Sahoo
AU - Sandrine Henri
AU - Bernard MALISSEN
AU - Andrew S. MacDonald
AU - Natalia Moncaut
AU - Santiago Zelenay
PY - 2026
DA - 2026/08/01
JO - Immunity
DO - 10.1016/j.immuni.2026.07.002
UR - https://doi.org/10.1016/j.immuni.2026.07.002
AB - Single-cell transcriptomics identifies a convergent activation state of conventional dendritic cells (cDCs) shared by type 1 and type 2 cDCs (cDC1s and cDC2s). These activated DCs (actDCs) are characterized by co-expression of T cell-stimulating and inhibitory molecules. Here, we examined the functional contribution of actDCs to anti-tumor immunity by developing mouse models that leverage CCR7 expression to conditionally label or ablate actDCs. The capacity of cDCs to stimulate tumor-specific cytotoxic T lymphocytes (CTLs) was restricted to the actDC state. cDC1- and cDC2-derived actDCs supported CTL priming through cross-presentation and cross-dressing, respectively, with the latter occurring in a cancer type-dependent manner. actDCs were required for the activation of naive CTLs in tumor-draining lymph nodes and for sustaining effector CTL function within tumors. Consequently, ablation of actDCs impaired spontaneous tumor control and responses to immune checkpoint blockade or adoptive T cell therapy. Thus, the actDC state emerges as a critical determinant of cDC-mediated anti-tumor immunity.
SN - 1074-7613
SN - 1097-4180
ER -