Immune-suppressive effects of interleukin-6 on T-cell-mediated anti-tumor immunity

Cancer Sci. 2018 Mar;109(3):523-530. doi: 10.1111/cas.13433. Epub 2017 Nov 16.

Abstract

Accompanied by the growing clinical applications of immunotherapy in the treatment of cancer patients, development of novel therapeutic approaches to reverse the immune-suppressive environment in cancer patients is eagerly anticipated, because the success of cancer immunotherapy is currently limited by immune-suppressive effects in tumor-bearing hosts. Interleukin (IL)-6, a pleotropic proinflammatory cytokine, participates in tumor cell-autonomous processes that are required for their survival and growth, and is therefore known as a poor prognostic factor in cancer patients. In addition, an emerging role of IL-6 in modulating multiple functions of immune cells including T cells, dendritic cells, and macrophages is responsible for the dysfunction of innate and adaptive immunity against tumors. Therefore, the IL-6-targeting approach is of value as a promising strategy for desensitization and prevention of immune-suppressive effects, and should be an effective treatment when combined with current immunotherapies. The aim of the present review is to discuss the immune-suppressive aspects of IL-6, notably with modification of T-cell functions in cancer patients, and their relationship to anti-tumor immune responses and cancer immunotherapy.

Keywords: T cell; Th1; cancer immunotherapy; immune suppression; interleukin-6.

Publication types

  • Review

MeSH terms

  • Animals
  • Antibodies, Monoclonal, Humanized / pharmacology
  • Antibodies, Monoclonal, Humanized / therapeutic use*
  • Clinical Trials as Topic
  • Drug Therapy
  • Humans
  • Immunotherapy
  • Interleukin-6 / antagonists & inhibitors
  • Interleukin-6 / metabolism*
  • Neoplasms / drug therapy*
  • Neoplasms / immunology
  • Signal Transduction
  • T-Lymphocytes / drug effects
  • T-Lymphocytes / immunology*

Substances

  • Antibodies, Monoclonal, Humanized
  • IL6 protein, human
  • Interleukin-6