1. Chemotherapy-induced antitumor immunity requires formyl peptide receptor 1.
- Author
-
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, and Kroemer G
- Subjects
- Alleles, Animals, Annexin A1 metabolism, Annexin A1 pharmacology, Breast Neoplasms drug therapy, Breast Neoplasms immunology, Cell Line, Tumor, Chemotherapy, Adjuvant, Colorectal Neoplasms drug therapy, Colorectal Neoplasms immunology, Dendritic Cells drug effects, Dendritic Cells immunology, Female, Humans, Immunity, Innate genetics, Leukocytes drug effects, Leukocytes immunology, Mice, Polymorphism, Single Nucleotide, Receptors, Formyl Peptide genetics, T-Lymphocytes immunology, Anthracyclines therapeutic use, Neoplasms drug therapy, Neoplasms immunology, Receptors, Formyl Peptide physiology
- 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., (Copyright © 2015, American Association for the Advancement of Science.)
- Published
- 2015
- Full Text
- View/download PDF