Biological effects of IL-15 on immune cells and its potential for the treatment of cancer

Int Immunopharmacol. 2021 Feb:91:107318. doi: 10.1016/j.intimp.2020.107318. Epub 2020 Dec 28.

Abstract

Interleukin-15 (IL-15) has recently emerged as a novel immunomodulatory cytokine in cancer immunotherapy. IL-15 has the potential to reject and destroy cancer cells in the tumor microenvironment by expanding and activating natural killer (NK), natural killer T (NKT), and memory (m) CD8+T cells. Due to the feasible outcomes obtained from preclinical studies and phase 1/2 clinical trials, IL-15-based therapy, including chimeric antigen receptor (CAR) T cell or CAR NK cell infusion following in vitro expansion in the presence of IL-15, used in combination with checkpoint inhibitors and other therapy may extend to clinical practice in the future. It is also important to understand the biological characteristics of IL-15 to ensure the maximal benefit of therapeutic strategies. Here, we summarize the current development of IL-15 in the following areas: anti-tumor mechanisms in the tumor microenvironment, advances in IL-15-based therapy itself or in combination with other methods, including biological agents, monoclonal antibodies, and adoptive immunotherapy.

Keywords: Cancer; Cytokine; IL-15; Superagonist; Tumor microenvironment.

Publication types

  • Review

MeSH terms

  • Adaptive Immunity / drug effects
  • Animals
  • Antineoplastic Agents / adverse effects
  • Antineoplastic Agents / therapeutic use*
  • CD8-Positive T-Lymphocytes / drug effects
  • CD8-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / metabolism
  • Cytotoxicity, Immunologic / drug effects
  • Humans
  • Immune System / drug effects*
  • Immune System / immunology
  • Immune System / metabolism
  • Immunity, Innate / drug effects
  • Immunotherapy* / adverse effects
  • Interleukin-15 / adverse effects
  • Interleukin-15 / therapeutic use*
  • Killer Cells, Natural / drug effects
  • Killer Cells, Natural / immunology
  • Killer Cells, Natural / metabolism
  • Lymphocytes, Tumor-Infiltrating / drug effects*
  • Lymphocytes, Tumor-Infiltrating / immunology
  • Lymphocytes, Tumor-Infiltrating / metabolism
  • Neoplasms / drug therapy*
  • Neoplasms / immunology
  • Neoplasms / metabolism
  • Neoplasms / pathology
  • Treatment Outcome
  • Tumor Microenvironment / drug effects*

Substances

  • Antineoplastic Agents
  • Interleukin-15