A TLR3 Ligand Reestablishes Chemotherapeutic Responses in the Context of FPR1 Deficiency
Abstract
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.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Feb 01, 2021
- Source ID
- 10.1158/2159-8290.cd-20-0465
Entities
People
- Allan Sauvat
- Aymeric Silvin
- Charles-antoine Dutertre
- Claire Mulot
- Cornelia Richter
- Erika Vacchelli
- Fabrice André
- Federico Pietrocola
- Florent Ginhoux
- Francesca Castoldi
- Gautier Stoll
- Giulia Cerrato
- Guido Kroemer
- Isabelle Martins
- Jessica Zucman-Rossi
- Jonathan G Pol
- Julie Le Naour
- Julien Taieb
- Juliette Paillet
- Khady Mangane
- Laurence Zitvogel
- Liwei Zhao
- Maria Chiara Maiuri
- Oliver Kepp
- Peng Liu
- Peter Vandenabeele
- Pierre Laurent-Puig
- Sandy Adjemian
- Suzette Delaloge
- Zoltán Szállási
- Zsófia Sztupinszki
Organizations
- Agence Nationale de la Recherche
- Agency for Science, Technology and Research
- Assistance Publique – Hôpitaux de Paris
- Cancéropôle PACA
- Congressionally Directed Medical Research Programs
- European Commission
- French National Institute of Health and Medical Research
- Ghent University
- Independent Research Fund Denmark
- Institut Gustave Roussy
- Institut National du Cancer
- Institut Universitaire de France
- Karolinska University Hospital
- National League Against Cancer
- Novo Nordisk Fonden
- Paris Descartes University
- Paris-Saclay University
- Peking Union Medical College
- Sorbonne University
- Technische Universität Dresden
- The Breast Cancer Research Foundation
- University of Paris