Chemotherapy-induced antitumor immunity requires formyl peptide receptor 1.
Fiche publication
Date publication
novembre 2015
Journal
Science (New York, N.Y.)
Auteurs
Membres identifiés du Cancéropôle Est :
Pr BORG Christophe, Dr LADOIRE Sylvain
Tous les auteurs :
Vacchelli E, Ma Y, Baracco EE, Sistigu A, Enot DP, Pietrocola F, Yang H, Adjemian S, Chaba K, Semeraro M, Signore M, De Ninno A, Lucarini V, Peschiaroli F, Businaro L, Gerardino A, Manic G, Ulas T, Günther P, Schultze JL, Kepp O, Stoll G, Lefebvre C, Mulot C, Castoldi F, Rusakiewicz S, Ladoire S, Apetoh L, Bravo-San Pedro JM, Lucattelli M, Delarasse C, Boige V, Ducreux M, Delaloge S, Borg C, André F, Schiavoni G, Vitale I, Laurent-Puig P, Mattei F, Zitvogel L, Kroemer G
Lien Pubmed
Résumé
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.
Mots clés
Alleles, Animals, Annexin A1, metabolism, Anthracyclines, therapeutic use, Breast Neoplasms, drug therapy, Cell Line, Tumor, Chemotherapy, Adjuvant, Colorectal Neoplasms, drug therapy, Dendritic Cells, drug effects, Female, Humans, Immunity, Innate, genetics, Leukocytes, drug effects, Mice, Neoplasms, drug therapy, Polymorphism, Single Nucleotide, Receptors, Formyl Peptide, genetics, T-Lymphocytes, immunology
Référence
Science. 2015 Nov;350(6263):972-8