| First Author | Le Naour J | Year | 2021 |
| Journal | Cancer Discov | Volume | 11 |
| Issue | 2 | Pages | 408-423 |
| PubMed ID | 33046534 | Mgi Jnum | J:301327 |
| Mgi Id | MGI:6505674 | Doi | 10.1158/2159-8290.CD-20-0465 |
| Citation | Le Naour J, et al. (2021) A TLR3 Ligand Reestablishes Chemotherapeutic Responses in the Context of FPR1 Deficiency. Cancer Discov 11(2):408-423 |
| abstractText | 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. |
