Cellular networks controlling T cell persistence in adoptive cell therapy

Nat Rev Immunol. 2021 Dec;21(12):769-784. doi: 10.1038/s41577-021-00539-6. Epub 2021 Apr 20.


The antitumour activity of endogenous or adoptively transferred tumour-specific T cells is highly dependent on their differentiation status. It is now apparent that less differentiated T cells compared with fully differentiated effector T cells have better antitumour therapeutic effects owing to their enhanced capacity to expand and their long-term persistence. In patients with cancer, the presence of endogenous or adoptively transferred T cells with stem-like memory or precursor phenotype correlates with improved therapeutic outcomes. Advances in our understanding of T cell differentiation states at the epigenetic and transcriptional levels have led to the development of novel methods to generate tumour-specific T cells - namely, chimeric antigen receptor T cells - that are more persistent and resistant to the development of dysfunction. These include the use of novel culture methods before infusion, modulation of transcriptional, metabolic and/or epigenetic programming, and strategies that fine-tune antigen receptor signalling. This Review discusses existing barriers and strategies to overcome them for successful T cell expansion and persistence in the context of adoptive T cell immunotherapy for solid cancers.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Cell- and Tissue-Based Therapy
  • Humans
  • Immunotherapy, Adoptive*
  • Lymphocyte Activation
  • Neoplasms / immunology*
  • Neoplasms / pathology
  • Neoplasms / therapy*
  • T-Lymphocytes / cytology*
  • T-Lymphocytes / immunology*