Enhancing adoptive T cell immunotherapy with microRNA therapeutics

Semin Immunol. 2016 Feb;28(1):45-53. doi: 10.1016/j.smim.2015.11.006. Epub 2015 Dec 20.

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.

Keywords: Adoptive cell transfer; CD8(+) T cells; Microrna (miRNA); T cell differentiation; Tumor immunotherapy.

Publication types

  • Review
  • Research Support, N.I.H., Intramural

MeSH terms

  • Animals
  • Cancer Vaccines / immunology*
  • Cell Differentiation / genetics
  • Cell Survival
  • Cytotoxicity, Immunologic
  • Humans
  • Immunity, Cellular / genetics
  • Immunotherapy, Adoptive / methods*
  • Lymphocyte Activation / genetics
  • MicroRNAs / genetics*
  • MicroRNAs / immunology
  • Neoplasms / immunology
  • Neoplasms / therapy*
  • RNA, Small Untranslated / genetics*
  • RNA, Small Untranslated / immunology
  • Receptors, Antigen, T-Cell / genetics
  • Receptors, Antigen, T-Cell / metabolism*
  • Signal Transduction
  • T-Lymphocytes / physiology*
  • T-Lymphocytes / transplantation

Substances

  • Cancer Vaccines
  • MicroRNAs
  • RNA, Small Untranslated
  • Receptors, Antigen, T-Cell