1. A TLR3 Ligand Reestablishes Chemotherapeutic Responses in the Context of FPR1 Deficiency
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Francesca Castoldi, Maria Chiara Maiuri, Julie Le Naour, Julien Taieb, Allan Sauvat, Suzette Delaloge, Charles-Antoine Dutertre, Jessica Zucman-Rossi, Juliette Paillet, Erika Vacchelli, Liwei Zhao, Giulia Cerrato, Guido Kroemer, Claire Mulot, Isabelle Martins, Oliver Kepp, Federico Pietrocola, Pierre Laurent-Puig, Aymeric Silvin, Florent Ginhoux, Fabrice Andre, Peng Liu, Laurence Zitvogel, Sandy Adjemian, Cornelia Richter, Zoltan Szallasi, Peter Vandenabeele, Zsofia Sztupinszki, Jonathan Pol, Gautier Stoll, Khady Mangane, Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité), Institut Gustave Roussy (IGR), Institut Universitaire de France (IUF), Ministère de l'Education nationale, de l’Enseignement supérieur et de la Recherche (M.E.N.E.S.R.), Universidade de São Paulo = University of São Paulo (USP), Boston Children's Hospital, Harvard Medical School [Boston] (HMS), Cancer Research and Personalized Medicine - CARPEM [Paris], Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Immunologie des tumeurs et immunothérapie (UMR 1015), Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Agency for science, technology and research [Singapore] (A*STAR), Singapore Immunology Network (SIgN), Biomedical Sciences Institute (BMSI), School of Medicine [Shanghai Jiaotong University], Shanghai Jiaotong University, Métabolisme, Cancer et Immunité (CRC - UMR_S 1138), Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité)-Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité)-École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), University of Oslo (UiO), Direction de la recherche [Gustave Roussy], Département de médecine oncologique [Gustave Roussy], Pathologie mammaire, Institut Gustave Roussy (IGR)-Institut Gustave Roussy (IGR), Immunologie anti-tumorale et immunothérapie des cancers (ITIC), Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, ANR-16-RHUS-0008,LUMIERE,LUMIERE(2016), European Project: 825410,ONCOBIOME, Le Naour, Julie, Liu, Peng, Zhao, Liwei, Adjemian, Sandy, Sztupinszki, Zsofia, Taieb, Julien, Mulot, Claire, Silvin, Aymeric, Dutertre, Charles-Antoine, Ginhoux, Florent, Sauvat, Allan, Cerrato, Giulia, Castoldi, Francesca, Martins, Isabelle, Stoll, Gautier, Paillet, Juliette, Mangane, Khady, Richter, Cornelia, Kepp, Oliver, Maiuri, Maria Chiara, Pietrocola, Federico, Vandenabeele, Peter, André, Fabrice, Delaloge, Suzette, Szallasi, Zoltan, Laurent-Puig, Pierre, Zucman-Rossi, Jessica, Zitvogel, Laurence, Pol, Jonathan G, Vacchelli, Erika, Kroemer, Guido, École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPC), Universidade de São Paulo (USP), Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPC)-Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPC)-École pratique des hautes études (EPHE), and Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPC)
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0301 basic medicine ,Anthracycline ,medicine.medical_treatment ,[SDV]Life Sciences [q-bio] ,Mice, Transgenic ,Ligands ,03 medical and health sciences ,Mice ,0302 clinical medicine ,Immune system ,Medicine ,Animals ,Humans ,ComputingMilieux_MISCELLANEOUS ,business.industry ,Pattern recognition receptor ,Wild type ,Immunotherapy ,Receptors, Formyl Peptide ,Toll-Like Receptor 3 ,Disease Models, Animal ,030104 developmental biology ,Cell Transformation, Neoplastic ,Poly I-C ,Oncology ,030220 oncology & carcinogenesis ,Cancer cell ,TLR3 ,Cancer research ,business ,Colorectal Neoplasms ,Annexin A1 - Abstract
For anthracycline-based chemotherapy to be immunogenic, dying cancer cells must release annexin A1 (ANXA1) that subsequently interacts with the pattern recognition receptor, formyl peptide receptor 1 (FPR1), on the surface of dendritic cells (DC). Approximately 30% of individuals bear loss-of-function alleles of FPR1, calling for strategies to ameliorate their anticancer immune response. Here, we show that immunotherapy with a ligand of Toll-like receptor-3, polyinosinic:polycytidylic acid (pIC), restores the deficient response to chemotherapy of tumors lacking ANXA1 developing in immunocompetent mice or those of normal cancers growing in FPR1-deficient mice. This effect was accompanied by improved DC- and T-lymphocyte–mediated anticancer immunity. Of note, carcinogen-induced breast cancers precociously developed in FPR1-deficient mice as compared with wild-type controls. A similar tendency for earlier cancer development was found in patients carrying the loss-of-function allele of FPR1. These findings have potential implications for the clinical management of FPR1-deficient patients. Significance: The loss-of-function variant rs867228 in FPR1, harbored by approximately 30% of the world population, is associated with the precocious manifestation of breast, colorectal, esophageal, and head and neck carcinomas. pIC restores deficient chemotherapeutic responses in mice lacking Fpr1, suggesting a personalized strategy for compensating for the FPR1 defect. This article is highlighted in the In This Issue feature, p. 211
- Published
- 2021
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