Chemotherapy-induced antitumor immunity requires formyl peptide receptor 1 PMID: 26516201

ADC Targets in Oncology

2026-04-10

Chemotherapy-induced antitumor immunity requires formyl peptide receptor 1

Science. 2015 Nov 20;350(6263):972-8. doi: 10.1126/science.aad0779.

Erika Vacchelli ¹ , Yuting Ma ² , Elisa E Baracco ³ , Antonella Sistigu ⁴ , David P Enot ⁵ , Federico Pietrocola ³ , Heng Yang ² , Sandy Adjemian ⁶ , Kariman Chaba ⁷ , Michaela Semeraro ⁸ , Michele Signore ⁹ , Adele De Ninno ¹⁰ , Valeria Lucarini ⁹ , Francesca Peschiaroli ⁹ , Luca Businaro ¹⁰ , Annamaria Gerardino ¹⁰ , Gwenola Manic ⁴ , Thomas Ulas ¹¹ , Patrick Günther ¹¹ , Joachim L Schultze ¹¹ , Oliver Kepp ¹ , Gautier Stoll ¹ , Céline Lefebvre ¹² , Claire Mulot ¹³ , Francesca Castoldi ¹⁴ , Sylvie Rusakiewicz ⁸ , Sylvain Ladoire ¹⁵ , Lionel Apetoh ¹⁵ , José Manuel Bravo-San Pedro ¹ , Monica Lucattelli ¹⁶ , Cécile Delarasse ¹⁷ , Valérie Boige ¹⁸ , Michel Ducreux ¹⁹ , Suzette Delaloge ²⁰ , Christophe Borg ²¹ , Fabrice André ²² , Giovanna Schiavoni ⁹ , Ilio Vitale ²³ , Pierre Laurent-Puig ²⁴ , Fabrizio Mattei ⁹ , Laurence Zitvogel ²⁵ , Guido Kroemer ²⁶

Affiliations

1. Gustave Roussy Cancer Campus, Villejuif, France. INSERM, U1138, Paris, France. Équipe 11 Labellisée par la Ligue Nationale Contre le Cancer, Centre de Recherche des Cordeliers, Paris, France. Université Paris Descartes, Sorbonne Paris Cité, Paris, France. Université Pierre et Marie Curie, Paris, France.
2. Gustave Roussy Cancer Campus, Villejuif, France. INSERM, U1138, Paris, France. Équipe 11 Labellisée par la Ligue Nationale Contre le Cancer, Centre de Recherche des Cordeliers, Paris, France. Université Paris Descartes, Sorbonne Paris Cité, Paris, France. Université Pierre et Marie Curie, Paris, France. Suzhou Institute of Systems Medicine, Suzhou, Jiangsu, China. Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
3. Gustave Roussy Cancer Campus, Villejuif, France. INSERM, U1138, Paris, France. Équipe 11 Labellisée par la Ligue Nationale Contre le Cancer, Centre de Recherche des Cordeliers, Paris, France. Faculté de Médecine, Université Paris-Saclay, Kremlin-Bicêtre, France.
4. Regina Elena National Cancer Institute, Rome, Italy.
5. Gustave Roussy Cancer Campus, Villejuif, France. INSERM, U1138, Paris, France. Équipe 11 Labellisée par la Ligue Nationale Contre le Cancer, Centre de Recherche des Cordeliers, Paris, France. Metabolomics and Cell Biology Platforms, Gustave Roussy Cancer Campus, Villejuif, France.
6. Gustave Roussy Cancer Campus, Villejuif, France. INSERM, U1138, Paris, France. Équipe 11 Labellisée par la Ligue Nationale Contre le Cancer, Centre de Recherche des Cordeliers, Paris, France.
7. Gustave Roussy Cancer Campus, Villejuif, France. INSERM, U1138, Paris, France. Équipe 11 Labellisée par la Ligue Nationale Contre le Cancer, Centre de Recherche des Cordeliers, Paris, France. Université Paris Descartes, Sorbonne Paris Cité, Paris, France.
8. Gustave Roussy Cancer Campus, Villejuif, France. INSERM, U1015, Villejuif, France. Center of Clinical Investigations in Biotherapies of Cancer (CICBT) 507, Villejuif, France.
9. Department of Hematology, Oncology, and Molecular Medicine, Istituto Superiore di Sanità, Rome, Italy.
10. Italian National Research Council, Institute for Photonics and Nanotechnology, Rome, Italy.
11. Genomics and Immunoregulation, Life and Medical Science Center Institute, University of Bonn, Germany.
12. Gustave Roussy Cancer Campus, Villejuif, France. INSERM, U981, Villejuif, France.
13. Université Paris Sorbonne Cité, UMRS 775, INSERM, Paris, France. INSERM U1147, Centre de Ressources Biologiques (CRB) EPIGENETIC, Paris, France.
14. Gustave Roussy Cancer Campus, Villejuif, France. INSERM, U1138, Paris, France. Équipe 11 Labellisée par la Ligue Nationale Contre le Cancer, Centre de Recherche des Cordeliers, Paris, France. Faculté de Médecine, Université Paris-Saclay, Kremlin-Bicêtre, France. Sotio, Prague, Czech Republic.
15. Department of Medical Oncology, Centre Georges-François Leclerc, Dijon, France. Université Bourgogne Franche-Comté, Dijon, France. Centre Georges François Leclerc, Dijon, France.
16. Department of Life Sciences, University of Siena, Siena, Italy.
17. Institut du Cerveau et de la Moelle Épinière, ICM CNRS UMR 7225 - INSERM U 1127 - UPMC-P6 UMR S 1127, Équipe Neurogénétique et Physiologie Hôpital de la Pitié-Salpêtrière, 47, Boulevard de l'Hôpital, 75013 Paris, France.
18. INSERM U1147, Centre de Ressources Biologiques (CRB) EPIGENETIC, Paris, France. Department of Medical Oncology, Gustave Roussy Cancer Campus, Villejuif Cedex, France.
19. Faculté de Médecine, Université Paris-Saclay, Kremlin-Bicêtre, France. Department of Medical Oncology, Gustave Roussy Cancer Campus, Villejuif Cedex, France.
20. INSERM, U981, Villejuif, France. Department of Breast Oncology, Gustave Roussy Cancer Campus, Villejuif, France.
21. University of Franche-Comté, INSERM 1098, France.
22. Gustave Roussy Cancer Campus, Villejuif, France. INSERM, U981, Villejuif, France. Department of Biology and Pathology, Gustave Roussy Cancer Campus, Villejuif, France. Department of Medical Oncology, Gustave Roussy Cancer Campus, Villejuif, France.
23. Regina Elena National Cancer Institute, Rome, Italy. Department of Biology, University of Rome "Tor Vergata," Rome, Italy.
24. Université Paris Sorbonne Cité, UMRS 775, INSERM, Paris, France. INSERM U1147, Centre de Ressources Biologiques (CRB) EPIGENETIC, Paris, France. Pôle de Biologie, Hôpital Européen Georges Pompidou, AP-HP, Paris, France.
25. Gustave Roussy Cancer Campus, Villejuif, France. Faculté de Médecine, Université Paris-Saclay, Kremlin-Bicêtre, France. INSERM, U1015, Villejuif, France. Center of Clinical Investigations in Biotherapies of Cancer (CICBT) 507, Villejuif, France. [email protected] [email protected].
26. Gustave Roussy Cancer Campus, Villejuif, France. INSERM, U1138, Paris, France. Équipe 11 Labellisée par la Ligue Nationale Contre le Cancer, Centre de Recherche des Cordeliers, Paris, France. Université Paris Descartes, Sorbonne Paris Cité, Paris, France. Université Pierre et Marie Curie, Paris, France. Metabolomics and Cell Biology Platforms, Gustave Roussy Cancer Campus, Villejuif, France. Pôle de Biologie, Hôpital Européen Georges Pompidou, AP-HP, Paris, France. Karolinska Institute, Department of Women's and Children's Health, Karolinska University Hospital, 17176 Stockholm, Sweden. [email protected] [email protected].

Abstract

Antitumor immunity driven by intratumoral dendritic cells contributes to the efficacy of anthracycline-based chemotherapy in Cancer. We identified a loss-of-function allele of the gene coding for formyl peptide receptor 1 (FPR1) that was associated with poor metastasis-free and overall survival in breast and colorectal Cancer patients receiving Adjuvant chemotherapy. The therapeutic effects of anthracyclines were abrogated in tumor-bearing Fpr1(-/-) mice due to impaired antitumor immunity. Fpr1-deficient dendritic cells failed to approach dying Cancer cells and, as a result, could not elicit antitumor T cell immunity. Experiments performed in a microfluidic device confirmed that FPR1 and its ligand, annexin-1, promoted stable interactions between dying Cancer cells and human or murine leukocytes. Altogether, these results highlight the importance of FPR1 in chemotherapy-induced Anticancer immune responses.