Molecular interactions between dying tumor cells and the innate immune system determine the efficacy of conventional anticancer therapies.
The efficacy of anticancer treatments is mostly assessed by their ability to directly inhibit the proliferation of tumor cells. Recently, we showed that tumor cell death triggered by chemotherapy or radiotherapy initiates an immunoadjuvant pathway that contributes to the success of cytotoxic treatments. The interaction of high mobility group box 1 protein (HMGB1) released from dying tumor cells with Toll-like receptor 4 (TLR4) on dendritic cells was required for the crosspresentation of tumor antigens and the promotion of tumor specific cytotoxic T-cell responses. Breast cancer patients harboring the loss-of-function Asp299Gly polymorphism of TLR4 relapsed earlier after receiving anthracycline-based chemotherapy. These data suggests that HMGB1- and TLR4-dependent immune responses elicited by conventional cancer treatment may increase the probability to achieve a durable therapeutic success.
Institut National de la Sante et de la Recherche Medicale, U805, Villejuif, France.
Lionel
L
Apetoh
Antoine
A
Tesniere
François
F
Ghiringhelli
Guido
G
Kroemer
Laurence
L
Zitvogel
D000818:Animals; D018943:Anthracyclines / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000235:genetics / Q000276:immunology / Q000473:pathology* / Q000628:therapy*; D024243:HMGB1 Protein / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007113:Immunity, Innate; D051379:Mice; D008819:Mice, Nude; D011110:Polymorphism, Genetic; D011485:Protein Binding; D011878:Radiotherapy; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000378:metabolism
D018943:Anthracyclines; D000970:Antineoplastic Agents; D024243:HMGB1 Protein; D051197:Toll-Like Receptor 4