Immunosenescence, inflammaging, and cancer immunotherapy efficacy

Expert Rev Anticancer Ther. 2022 Sep;22(9):915-926. doi: 10.1080/14737140.2022.2098718. Epub 2022 Jul 14.

Abstract

Introduction: Immunosenescence is a progressive remodeling of immune functions associated with a decreased ability of the immune system to set up an efficient immune response, both innate and adaptive, with an increase of highly differentiated T cells at the expense of naive T cells. The incidence and prevalence of most cancers increase with age, which can partly be explained by tumor escape mechanisms and decreased immunosurveillance. Aging is also associated with inflammaging, a low-grade proinflammatory state characterized by an increase in inflammatory mediators. Anti-cancer immunotherapy has profoundly changed the landscape of oncology therapy in the last 10 years. Modern T-cell targeted therapies such as bispecific T cell engagers, CAR-T cells, or immune checkpoint blockers may be theoretically affected by immunosenescence or inflammaging.

Areas covered: A bibliographic review through PubMed and Embase was carried out using the following search terms: 'immunosenescence,' 'immunotherapy,' 'inflammaging,' 'bispecific antibodies,' 'CAR-T cells,' 'immune checkpoint blockers,' and 'older patients.'

Expert opinion: This review explores the potential impact of immunosenescence and inflammaging on anti-cancer immunotherapy and therapeutic strategies that could counter immune senescence. A more dedicated research on immunosenescence biomarkers in future clinical trials is warranted for the development of new, more effective and safer therapies.

Keywords: CART cells; Immunosenescence; bispecific T-cell engagers; immune checkpoint inhibitors; inflammaging; older patients.

Publication types

  • Review

MeSH terms

  • Aging / physiology
  • Humans
  • Immune Checkpoint Inhibitors
  • Immunosenescence* / physiology
  • Immunotherapy
  • Inflammation / therapy
  • Neoplasms* / therapy

Substances

  • Immune Checkpoint Inhibitors