Intratumoral delivery of FLT3L with CXCR3/CCR5 ligands promotes XCR1+ cDC1 infiltration and activates anti-tumor immunity

intratumoral-delivery-of-flt3l-with-cxcr3/ccr5-ligands-promotes-xcr1+-cdc1-infiltration-and-activates-anti-tumor-immunity
Intratumoral delivery of FLT3L with CXCR3/CCR5 ligands promotes XCR1+ cDC1 infiltration and activates anti-tumor immunity

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Data supporting the findings of this study are available within the article, Supplementary Information or Source data file. Source data are provided as a Source data file. Source data are provided with this paper.

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Acknowledgements

P.G. is a CNRS investigator (Centre National de la Recherche Scientifique). This work was supported by Fonds National Suisse (SINGERGIA SNF CRSII5_202246/1, P.G., S.H.), INSERM transfert CO-POC grant (P.G.), Agence Nationale pour la Recherche (ANR-17-CE11-0001-01 and ANR-18-IDEX-0001, P.G.), La Ligue contre le cancer (P.G.), Institut National du Cancer INCA (PL-BIO22-147, P.G.), Fondation pour la Recherche Médicale (EQU202203014687, P.G.), Fondation pour la Recherche sur le Cancer ARC (PJA2021060003913, P.G.) and the Pasteur Institute. We would like to thank the staff of the flow cytometry and the animal facility platforms from the CRI (Centre de Recherche sur l’Inflammation, Faculté de Médecine, Bichat) and from the Pasteur Institute for all the work, help and support in most of the experiments presented in this paper. We also like to thank the staff from the histopathology core facility from the Pasteur Institute for the liver H&E images. We thank Rémy Yim (Human Disease Models Core Facility, Institut Pasteur, Université Paris Cité, 75015 Paris, France), the Human Disease Models Core Facility (Institut Pasteur, Paris) and the CRB-Banque de Sang de Cordon, AP-HP, Hôpital Saint-Louis, Unité de Thérapie Cellulaire, Paris, France for the experiments on the BRGSF reconstituted mice. We thank the units U1149 and U1016 of Institut National de la Santé et de la Recherche Médicale. We thank the unit UMR3738 of the Centre National de la Recherche at the Pasteur Institute. We also would like to thank Laleh Majlessi for providing the NanoLuciferase vector, Alexandre Boissonnas (Sorbonne Université, INSERM U1135, CNRS, Centre d’Immunologie et des Maladies Infectieuses, Cimi-Paris, Paris 75013, France), Dr. Philippe Bousso (Dynamics of Immune Responses Unit, Institut Pasteur, Université de Paris Cité, INSERM U1223, F-75015 Paris, France), Loredana Saveanu and Dr. Laurie Menger (Inserm U1015, Gustave Roussy Cancer Campus, Villejuif 94800, France) for providing us various cell lines, Marc Dalod, Dr. Tessa Bergsbaken (Department of Pathology, Immunology and Laboratory Medicine, Center for Immunity and Inflammation, Rutgers New Jersey Medical School, Rutgers-The State University of New Jersey, Newark, NJ) and Dr. Sebastian Amigorena (Institut Curie, PSL University, INSERM U932, Immunity and Cancer, Paris, France) for providing us mice strains and Dr. Geneviève Marcelin (Sorbonne Université, INSERM U1269, Nutrition and obesities: systemic approach research group, Nutriomics, Paris F-75013, France) for providing us protocols.

Author information

Author notes

  1. These authors contributed equally: Louise Gorline, Fillipe Luiz Rosa do Carmo.

Authors and Affiliations

  1. Dendritic Cells and Adaptive Immunity Unit, Immunology Department, Institut Pasteur, Université de Paris Cité, Paris, France

    Louise Gorline, Fillipe Luiz Rosa do Carmo, Jérémie Bornères, Nathan Vaudiau, Aurélie Semervil, Aboubacar Sidiki K Coulibaly, Natacha Jugniot, Ikrame Haddar & Pierre Guermonprez

  2. CNRS UMR3738, Developmental Biology and Stem Cells, Institut Pasteur, Université de Paris Cité, Paris, France

    Louise Gorline, Fillipe Luiz Rosa do Carmo, Jérémie Bornères, Nathan Vaudiau, Aurélie Semervil, Aboubacar Sidiki K Coulibaly, Natacha Jugniot, Ikrame Haddar & Pierre Guermonprez

  3. Centre for Vaccine and Immunotherapy, Institut Pasteur, Paris, France

    Louise Gorline, Fillipe Luiz Rosa do Carmo, Jérémie Bornères, Nathan Vaudiau, Aurélie Semervil, Aboubacar Sidiki K Coulibaly, Natacha Jugniot, Ikrame Haddar, James P. Di Santo & Pierre Guermonprez

  4. Laboratory of Tumor Inflammation and Angiogenesis, Center for Cancer Biology, VIB, Leuven, Belgium

    Pierre Bourdely

  5. INSERM UMR 1016, CNRS UMR 8104, Institut Cochin, Université Paris Cité, Paris, France

    Pierre Bourdely, Aurélie Semervil, Zeina Abou Nader, Judith Weber & Julie Helft

  6. Bichat Medical School, INSERM UMR1149, CNRS EMR8252, Université Paris Cité, Paris, France

    Mathias Vetillard, Agathe Ok & Loredana Saveanu

  7. Department of Pathology and Immunology, Geneva Medical School, Geneva, Switzerland

    Mathilde Bausart, Flavia Fico & Stéphanie Hugues

  8. Human Disease Models Core Facility, Institut Pasteur, Université Paris Cité, Paris, France

    Oriane Fiquet, Marine Andrade & Mathilde Dusseaux

  9. Nutrition and Obesity: Systemic Approaches, Inserm, Sorbonne University, Paris, France

    Dicken Fardol & Emmanuel L. Gautier

  10. Inserm U1015, Institut Gustave Roussy, Université Paris-Saclay, Villejuif, France

    Hannah Theobald & Florent Ginhoux

  11. Inserm Transfert, Paris, France

    Matthieu Collin & Joseph Calmette

  12. Deparment of Cellular Immunology, International Centre for Genetic Engineering and Biotechnology, Trieste, Italy

    Giorgio Anselmi

  13. Virology Department, Pasteur-TheraVectys Joint Laboratory, Institut Pasteur, Université Paris Cité, Paris, France

    Laleh Majlessi

  14. Centre d’Immunologie de Marseille-Luminy, CIML, CNRS, INSERM, Aix Marseille Université, Marseille, France

    Marc Dalod

  15. Immunology Department, Immunité Innée, Institut Pasteur, Paris, France

    James P. Di Santo

Authors

  1. Louise Gorline
  2. Fillipe Luiz Rosa do Carmo
  3. Pierre Bourdely
  4. Jérémie Bornères
  5. Nathan Vaudiau
  6. Aurélie Semervil
  7. Mathias Vetillard
  8. Aboubacar Sidiki K Coulibaly
  9. Natacha Jugniot
  10. Agathe Ok
  11. Mathilde Bausart
  12. Oriane Fiquet
  13. Marine Andrade
  14. Dicken Fardol
  15. Ikrame Haddar
  16. Zeina Abou Nader
  17. Judith Weber
  18. Hannah Theobald
  19. Matthieu Collin
  20. Joseph Calmette
  21. Giorgio Anselmi
  22. Flavia Fico
  23. Florent Ginhoux
  24. Laleh Majlessi
  25. Emmanuel L. Gautier
  26. Loredana Saveanu
  27. Julie Helft
  28. Marc Dalod
  29. Mathilde Dusseaux
  30. James P. Di Santo
  31. Stéphanie Hugues
  32. Pierre Guermonprez

Contributions

Conceptualization: S.H., P.G. Investigation: L.G., F.L.R.D.C., P.B., J.B., N.V., A.S., M.V., A.S.K.C., N.J., A.O., M.B., O.F., M.A., D.F., I.H., Z.A.N., J.W., H.T., G.A., F.F. Resources: F.G., L.M., E.L.G., L.S., J.H., MDalod, MDusseaux, J.P.D.S., S.H., P.G. Writing: L.G., F.L.R.D.C., S.H., P.G., Supervision: S.H., P.G. Funding acquisition: M.C., J.C., J.H., S.H., P.G.

Corresponding author

Correspondence to Pierre Guermonprez.

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The authors declare no competing interests.

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Nature Communications thanks Moutih Rafei and the other anonymous reviewer(s) for their contribution to the peer review of this work. A peer review file is available.

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Gorline, L., do Carmo, F.L.R., Bourdely, P. et al. Intratumoral delivery of FLT3L with CXCR3/CCR5 ligands promotes XCR1+ cDC1 infiltration and activates anti-tumor immunity. Nat Commun (2025). https://doi.org/10.1038/s41467-025-68018-3

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