Chemotherapy-induced antitumor immunity requires formyl peptide receptor 1
Menée in vitro et in vivo, cette étude met en évidence des mécanismes de nature immunitaire par lesquels le récepteur 1 des peptides formyles contribue à l'efficacité d'une chimiothérapie à base d'anthracyclines pour le traitement d'un cancer du sein ou du côlon-rectum
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.