Immune Aging and Immunotherapy in Cancer

Int J Mol Sci. 2021 Jun 29;22(13):7016. doi: 10.3390/ijms22137016.


Immune functions decline as we age, while the incidence of cancer rises. The advent of immune checkpoint blockade (ICB) has not only revolutionized cancer therapy, but also spawned great interest in identifying predictive biomarkers, since only one third of patients show treatment response. The aging process extensively affects the adaptive immune system and thus T cells, which are the main target of ICB. In this review, we address age-related changes regarding the adaptive immune system with a focus on T cells and their implication on carcinogenesis and ICB. Differences between senescence, exhaustion, and anergy are defined and current knowledge, treatment strategies, and studies exploring T cell aging as a biomarker for ICB are discussed. Finally, novel approaches to improve immunotherapies and to identify biomarkers of response to ICB are presented and their potential is assessed in a comparative analysis.

Keywords: T cells; aging; biomarker; cancer; exhaustion; immune checkpoint inhibitors; senescence.

Publication types

  • Review

MeSH terms

  • Adaptive Immunity / physiology
  • Aging / immunology*
  • Humans
  • Immune Checkpoint Inhibitors / therapeutic use
  • Immunotherapy* / adverse effects
  • Immunotherapy* / methods
  • Neoplasms* / immunology
  • Neoplasms* / pathology
  • Neoplasms* / therapy
  • T-Lymphocytes / immunology
  • T-Lymphocytes / physiology


  • Immune Checkpoint Inhibitors