title: Chemotherapy-induced antitumor immunity requires formyl peptide receptor 1.
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.
authors.affiliation: 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.
authors.forename: Erika
authors.initials: E
authors.lastname: Vacchelli
authors.affiliation: 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.
authors.forename: Yuting
authors.initials: Y
authors.lastname: Ma
authors.affiliation: 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.
authors.forename: Elisa E
authors.initials: EE
authors.lastname: Baracco
authors.affiliation: Regina Elena National Cancer Institute, Rome, Italy.
authors.forename: Antonella
authors.initials: A
authors.lastname: Sistigu
authors.affiliation: 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.
authors.forename: David P
authors.initials: DP
authors.lastname: Enot
authors.affiliation: 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.
authors.forename: Federico
authors.initials: F
authors.lastname: Pietrocola
authors.affiliation: 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.
authors.forename: Heng
authors.initials: H
authors.lastname: Yang
authors.affiliation: 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.
authors.forename: Sandy
authors.initials: S
authors.lastname: Adjemian
authors.affiliation: 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.
authors.forename: Kariman
authors.initials: K
authors.lastname: Chaba
authors.affiliation: Gustave Roussy Cancer Campus, Villejuif, France. INSERM, U1015, Villejuif, France. Center of Clinical Investigations in Biotherapies of Cancer (CICBT) 507, Villejuif, France.
authors.forename: Michaela
authors.initials: M
authors.lastname: Semeraro
authors.affiliation: Department of Hematology, Oncology, and Molecular Medicine, Istituto Superiore di Sanità, Rome, Italy.
authors.forename: Michele
authors.initials: M
authors.lastname: Signore
authors.affiliation: Italian National Research Council, Institute for Photonics and Nanotechnology, Rome, Italy.
authors.forename: Adele
authors.initials: A
authors.lastname: De Ninno
authors.affiliation: Department of Hematology, Oncology, and Molecular Medicine, Istituto Superiore di Sanità, Rome, Italy.
authors.forename: Valeria
authors.initials: V
authors.lastname: Lucarini
authors.affiliation: Department of Hematology, Oncology, and Molecular Medicine, Istituto Superiore di Sanità, Rome, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Peschiaroli
authors.affiliation: Italian National Research Council, Institute for Photonics and Nanotechnology, Rome, Italy.
authors.forename: Luca
authors.initials: L
authors.lastname: Businaro
authors.affiliation: Italian National Research Council, Institute for Photonics and Nanotechnology, Rome, Italy.
authors.forename: Annamaria
authors.initials: A
authors.lastname: Gerardino
authors.affiliation: Regina Elena National Cancer Institute, Rome, Italy.
authors.forename: Gwenola
authors.initials: G
authors.lastname: Manic
authors.affiliation: Genomics and Immunoregulation, Life and Medical Science Center Institute, University of Bonn, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Ulas
authors.affiliation: Genomics and Immunoregulation, Life and Medical Science Center Institute, University of Bonn, Germany.
authors.forename: Patrick
authors.initials: P
authors.lastname: Günther
authors.affiliation: Genomics and Immunoregulation, Life and Medical Science Center Institute, University of Bonn, Germany.
authors.forename: Joachim L
authors.initials: JL
authors.lastname: Schultze
authors.affiliation: 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.
authors.forename: Oliver
authors.initials: O
authors.lastname: Kepp
authors.affiliation: 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.
authors.forename: Gautier
authors.initials: G
authors.lastname: Stoll
authors.affiliation: Gustave Roussy Cancer Campus, Villejuif, France. INSERM, U981, Villejuif, France.
authors.forename: Céline
authors.initials: C
authors.lastname: Lefebvre
authors.affiliation: Université Paris Sorbonne Cité, UMRS 775, INSERM, Paris, France. INSERM U1147, Centre de Ressources Biologiques (CRB) EPIGENETIC, Paris, France.
authors.forename: Claire
authors.initials: C
authors.lastname: Mulot
authors.affiliation: 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.
authors.forename: Francesca
authors.initials: F
authors.lastname: Castoldi
authors.affiliation: Gustave Roussy Cancer Campus, Villejuif, France. INSERM, U1015, Villejuif, France. Center of Clinical Investigations in Biotherapies of Cancer (CICBT) 507, Villejuif, France.
authors.forename: Sylvie
authors.initials: S
authors.lastname: Rusakiewicz
authors.affiliation: Department of Medical Oncology, Centre Georges-François Leclerc, Dijon, France. Université Bourgogne Franche-Comté, Dijon, France. Centre Georges François Leclerc, Dijon, France.
authors.forename: Sylvain
authors.initials: S
authors.lastname: Ladoire
authors.affiliation: Department of Medical Oncology, Centre Georges-François Leclerc, Dijon, France. Université Bourgogne Franche-Comté, Dijon, France. Centre Georges François Leclerc, Dijon, France.
authors.forename: Lionel
authors.initials: L
authors.lastname: Apetoh
authors.affiliation: 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.
authors.forename: José Manuel
authors.initials: JM
authors.lastname: Bravo-San Pedro
authors.affiliation: Department of Life Sciences, University of Siena, Siena, Italy.
authors.forename: Monica
authors.initials: M
authors.lastname: Lucattelli
authors.affiliation: 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.
authors.forename: Cécile
authors.initials: C
authors.lastname: Delarasse
authors.affiliation: INSERM U1147, Centre de Ressources Biologiques (CRB) EPIGENETIC, Paris, France. Department of Medical Oncology, Gustave Roussy Cancer Campus, Villejuif Cedex, France.
authors.forename: Valérie
authors.initials: V
authors.lastname: Boige
authors.affiliation: Faculté de Médecine, Université Paris-Saclay, Kremlin-Bicêtre, France. Department of Medical Oncology, Gustave Roussy Cancer Campus, Villejuif Cedex, France.
authors.forename: Michel
authors.initials: M
authors.lastname: Ducreux
authors.affiliation: INSERM, U981, Villejuif, France. Department of Breast Oncology, Gustave Roussy Cancer Campus, Villejuif, France.
authors.forename: Suzette
authors.initials: S
authors.lastname: Delaloge
authors.affiliation: University of Franche-Comté, INSERM 1098, France.
authors.forename: Christophe
authors.initials: C
authors.lastname: Borg
authors.affiliation: 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.
authors.forename: Fabrice
authors.initials: F
authors.lastname: André
authors.affiliation: Department of Hematology, Oncology, and Molecular Medicine, Istituto Superiore di Sanità, Rome, Italy.
authors.forename: Giovanna
authors.initials: G
authors.lastname: Schiavoni
authors.affiliation: Regina Elena National Cancer Institute, Rome, Italy. Department of Biology, University of Rome "Tor Vergata," Rome, Italy.
authors.forename: Ilio
authors.initials: I
authors.lastname: Vitale
authors.affiliation: 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.
authors.forename: Pierre
authors.initials: P
authors.lastname: Laurent-Puig
authors.affiliation: Department of Hematology, Oncology, and Molecular Medicine, Istituto Superiore di Sanità, Rome, Italy.
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Mattei
authors.affiliation: 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. kroemer@orange.fr laurence.zitvogel@gustaveroussy.fr.
authors.forename: Laurence
authors.initials: L
authors.lastname: Zitvogel
authors.affiliation: 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. kroemer@orange.fr laurence.zitvogel@gustaveroussy.fr.
authors.forename: Guido
authors.initials: G
authors.lastname: Kroemer
mesh_terms: D000483:Alleles; D000818:Animals; D017305:Annexin A1 / Q000378:metabolism / Q000494:pharmacology; D018943:Anthracyclines / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy / Q000276:immunology; D045744:Cell Line, Tumor; D017024:Chemotherapy, Adjuvant; D015179:Colorectal Neoplasms / Q000188:drug therapy / Q000276:immunology; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology; D005260:Female; D006801:Humans; D007113:Immunity, Innate / Q000235:genetics; D007962:Leukocytes / Q000187:drug effects / Q000276:immunology; D051379:Mice; D009369:Neoplasms / Q000188:drug therapy* / Q000276:immunology*; D020641:Polymorphism, Single Nucleotide; D044042:Receptors, Formyl Peptide / Q000235:genetics / Q000502:physiology*; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D017305:Annexin A1; D018943:Anthracyclines; C469986:FPR1 protein, human; C469988:Fpr1 protein, mouse; D044042:Receptors, Formyl Peptide