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RESEARCH PRODUCT

Fasting renders immunotherapy effective against low-immunogenic breast cancer while reducing side effects

Salvatore CortellinoAlessandro RaveaneClaudia ChiodoniGloria DelfantiFederica PisatiVanessa SpagnoloEuplio ViscoGiuseppe FragaleFederica FerranteSerena MagniFabio IannelliFederica ZanardiGiulia CasoratiFrancesco BertoliniPaolo DellabonaMario P. ColomboClaudio TripodoValter D. Longo

subject

Tumor MicroenvironmentHumansTriple Negative Breast NeoplasmsFastingImmunotherapySettore MED/08 - Anatomia PatologicaGlycolysisnutrition triple-negative breast cancer CP: Cancer CP: Immunology fasting fasting-mimicking diet immunotherapy inflammationB7-H1 AntigenGeneral Biochemistry Genetics and Molecular Biology

description

Immunotherapy is improving the prognosis and survival of cancer patients, but despite encouraging out-comes in different cancers, the majority of tumors are resistant to it, and the immunotherapy combinations are often accompanied by severe side effects. Here, we show that a periodic fasting-mimicking diet (FMD) can act on the tumor microenvironment and increase the efficacy of immunotherapy (anti-PD-L1 and anti-OX40) against the poorly immunogenic triple-negative breast tumors (TNBCs) by expanding early exhausted effector T cells, switching the cancer metabolism from glycolytic to respiratory, and reducing collagen depo-sition. Furthermore, FMD reduces the occurrence of immune-related adverse events (irAEs) by preventing the hyperactivation of the immune response. These results indicate that FMD cycles have the potential to enhance the efficacy of anti-cancer immune responses, expand the portion of tumors sensitive to immuno-therapy, and reduce its side effects.

yearjournalcountryeditionlanguage
2022-08-23Cell Reports
https://doi.org/10.1016/j.celrep.2022.111256