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

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