title: Enhancing adoptive T cell immunotherapy with microRNA therapeutics.
abstract: Adoptive T cell-based immunotherapies can mediate complete and durable regressions in patients with advanced cancer, but current response rates remain inadequate. Maneuvers to improve the fitness and antitumor efficacy of transferred T cells have been under extensive exploration in the field. Small non-coding microRNAs have emerged as critical modulators of immune system homeostasis and T cell immunity. Here, we summarize recent advances in our understanding of the role of microRNAs in regulating T cell activation, differentiation, and function. We also discuss how microRNA therapeutics could be employed to fine-tune T cell receptor signaling and enhance T cell persistence and effector functions, paving the way for the next generation of adoptive immunotherapies.
authors.affiliation: Experimental Transplantation and Immunology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, 10 Center Drive, Bethesda, MD, USA. Electronic address: jiyun@mail.nih.gov.
authors.forename: Yun
authors.initials: Y
authors.lastname: Ji
authors.affiliation: Experimental Transplantation and Immunology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, 10 Center Drive, Bethesda, MD, USA.
authors.forename: James D
authors.initials: JD
authors.lastname: Hocker
authors.affiliation: Experimental Transplantation and Immunology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, 10 Center Drive, Bethesda, MD, USA. Electronic address: gattinol@mail.nih.gov.
authors.forename: Luca
authors.initials: L
authors.lastname: Gattinoni
mesh_terms: D000818:Animals; D019496:Cancer Vaccines / Q000276:immunology*; D002454:Cell Differentiation / Q000235:genetics; D002470:Cell Survival; D003602:Cytotoxicity, Immunologic; D006801:Humans; D007111:Immunity, Cellular / Q000235:genetics; D016219:Immunotherapy, Adoptive / Q000379:methods*; D008213:Lymphocyte Activation / Q000235:genetics; D035683:MicroRNAs / Q000235:genetics* / Q000276:immunology; D009369:Neoplasms / Q000276:immunology / Q000628:therapy*; D058727:RNA, Small Untranslated / Q000235:genetics* / Q000276:immunology; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000502:physiology* / Q000637:transplantation
chemical_list: D019496:Cancer Vaccines; D035683:MicroRNAs; D058727:RNA, Small Untranslated; D011948:Receptors, Antigen, T-Cell
keywords: Adoptive cell transfer; CD8(+) T cells; Microrna (miRNA); T cell differentiation; Tumor immunotherapy