title: Toll-like receptor 4-dependent contribution of the immune system to anticancer chemotherapy and radiotherapy.
abstract: Conventional cancer treatments rely on radiotherapy and chemotherapy. Such treatments supposedly mediate their effects via the direct elimination of tumor cells. Here we show that the success of some protocols for anticancer therapy depends on innate and adaptive antitumor immune responses. We describe in both mice and humans a previously unrecognized pathway for the activation of tumor antigen-specific T-cell immunity that involves secretion of the high-mobility-group box 1 (HMGB1) alarmin protein by dying tumor cells and the action of HMGB1 on Toll-like receptor 4 (TLR4) expressed by dendritic cells (DCs). During chemotherapy or radiotherapy, DCs require signaling through TLR4 and its adaptor MyD88 for efficient processing and cross-presentation of antigen from dying tumor cells. Patients with breast cancer who carry a TLR4 loss-of-function allele relapse more quickly after radiotherapy and chemotherapy than those carrying the normal TLR4 allele. These results delineate a clinically relevant immunoadjuvant pathway triggered by tumor cell death.
authors: Institut Gustave Roussy (IGR), 39 rue Camille Desmoulins, F-94805 Villejuif, France.
authors: Lionel
authors: L
authors: Apetoh
authors: François
authors: F
authors: Ghiringhelli
authors: Antoine
authors: A
authors: Tesniere
authors: Michel
authors: M
authors: Obeid
authors: Carla
authors: C
authors: Ortiz
authors: Alfredo
authors: A
authors: Criollo
authors: Grégoire
authors: G
authors: Mignot
authors: M Chiara
authors: MC
authors: Maiuri
authors: Evelyn
authors: E
authors: Ullrich
authors: Patrick
authors: P
authors: Saulnier
authors: Huan
authors: H
authors: Yang
authors: Sebastian
authors: S
authors: Amigorena
authors: Bernard
authors: B
authors: Ryffel
authors: Franck J
authors: FJ
authors: Barrat
authors: Paul
authors: P
authors: Saftig
authors: Francis
authors: F
authors: Levi
authors: Rosette
authors: R
authors: Lidereau
authors: Catherine
authors: C
authors: Nogues
authors: Jean-Paul
authors: JP
authors: Mira
authors: Agnès
authors: A
authors: Chompret
authors: Virginie
authors: V
authors: Joulin
authors: Françoise
authors: F
authors: Clavel-Chapelon
authors: Jean
authors: J
authors: Bourhis
authors: Fabrice
authors: F
authors: André
authors: Suzette
authors: S
authors: Delaloge
authors: Thomas
authors: T
authors: Tursz
authors: Guido
authors: G
authors: Kroemer
authors: Laurence
authors: L
authors: Zitvogel
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001859:Bone Neoplasms / Q000188:drug therapy; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000188:drug therapy / Q000532:radiotherapy; D004195:Disease Models, Animal; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D009369:Neoplasms / Q000188:drug therapy* / Q000532:radiotherapy*; D009944:Organoplatinum Compounds / Q000627:therapeutic use; D012516:Osteosarcoma / Q000188:drug therapy; D011725:Pyridines / Q000627:therapeutic use; D051197:Toll-Like Receptor 4 / Q000276:immunology*
chemical_list: D000970:Antineoplastic Agents; D009944:Organoplatinum Compounds; D011725:Pyridines; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4; C431073:oxiplatin