IL-6 as a major regulator of MDSC activity and possible target for cancer immunotherapy

Cell Immunol. 2021 Jan:359:104254. doi: 10.1016/j.cellimm.2020.104254. Epub 2020 Nov 29.

Abstract

Myeloid-derived suppressor cells (MDSC) are generated during tumor progression and suppress the anti-tumor functions of T and natural killer (NK) cells. Their enrichment is associated with a bad prognosis and a worse outcome of immunotherapy in cancer patients. The cytokine interleukin (IL)-6 was found to be a crucial regulator of MDSC accumulation and activation as well as a factor, stimulating tumor cell proliferation, survival, invasiveness and metastasis. Accordingly, IL-6 can serve as a negative prognostic marker in cancer. On the other hand, this cytokine is also involved in T cell activation. This review discusses the pleiotropic effects of IL-6 on immune cell populations that are critical for tumor development, such as MDSC and T cells, and summarizes the data on targeting IL-6 or IL-6 receptor (IL-6R) for tumor immunotherapy to block MDSC-mediated immunosuppression in cancer patients.

Keywords: Cancer; IL-6; Immunosuppression; Immunotherapy; Myeloid-derived suppressor cells.

Publication types

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

MeSH terms

  • Cell Proliferation / drug effects
  • Cytokines / immunology
  • Humans
  • Immune Tolerance / immunology
  • Immunosuppression Therapy / methods
  • Immunotherapy / methods*
  • Immunotherapy / trends
  • Interleukin-6 / immunology
  • Interleukin-6 / metabolism*
  • Interleukin-6 / therapeutic use
  • Killer Cells, Natural / immunology
  • Lymphocyte Activation / immunology
  • Myeloid-Derived Suppressor Cells / immunology*
  • Myeloid-Derived Suppressor Cells / metabolism
  • Neoplasms / immunology
  • Neoplasms / therapy
  • Prognosis
  • Receptors, Interleukin-6 / immunology
  • Receptors, Interleukin-6 / metabolism
  • T-Lymphocytes / immunology

Substances

  • Cytokines
  • Interleukin-6
  • Receptors, Interleukin-6