期刊
CANCER RESEARCH
卷 76, 期 11, 页码 3122-3126出版社
AMER ASSOC CANCER RESEARCH
DOI: 10.1158/0008-5472.CAN-16-0294
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资金
- Ligue Nationale contre le Cancer (Equipes labellisees)
- Site de Recherche Integree sur le Cancer (IRIC) Socrates
- ISREC Foundation
- Agence National de la Recherche (ANR) - Projets blancs
- ANR under the frame of E-Rare-2
- ERA-Net for Research on Rare Diseases
- Association pour la recherche sur le cancer (ARC)
- European Commission (ArtForce)
- European Research Council Advanced Investigator Grant
- Institut Universitaire de France
- Fondation pour la Recherche Medicale (FRM)
- Institut National du Cancer (INCa)
- Fondation de France
- Canceropole Ile-de-France
- Fondation Bettencourt-Schueller
- European Research Council (ERC)
- LeDucq Foundation
- LabEx Immuno-Oncology
- SIRIC Stratified Oncology Cell DNA Repair and Tumor Immune Elimination (SOCRATE)
- SIRIC Cancer Research and Personalized Medicine (CARPEM)
- Paris Alliance of Cancer Research Institutes (PACRI)
Pattern recognition receptors allow the innate immune system to perceive the presence of microbial products and to launch the first steps of the defense response. Some pattern recognition receptors also sense endogenous ligands that are released from uninfected dying cells, thereby activating immune responses against dead-cell antigens. This applies to toll-like receptors 3 and 4 (TLR3, TLR4), which sense double-stranded RNA and high-mobility group protein B1 (HMGB1), respectively, as well as to formyl peptide receptor-1 (FPR1), which interacts with Annexin A1 (ANXA1) from dead cells. Breast cancer patients who bear loss-of-function alleles in TLR3, TLR4, and FPR1 exhibit a reduced metastasis-free and overall survival after treatment with anthracycline-based adjuvant chemotherapy. These genetic defects are epistatic with respect to each other, suggesting that they act on the same pathway, linking chemotherapy to a therapeutically relevant anticancer immune response. Loss-of-function alleles in TLR4 and FPR1 also affect the prognosis of colorectal cancer patients treated with oxaliplatin-based chemotherapy. Altogether, these results support the idea that conventional anticancer treatments rely on stimulation of anticancer immune responses to become fully efficient. (C) 2016 AACR.
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