Signal transducer and activator of transcription 3 in myeloid-derived suppressor cells: an opportunity for cancer therapy

Oncotarget. 2016 Jul 5;7(27):42698-42715. doi: 10.18632/oncotarget.8311.

Abstract

Cancer progression is in part determined by interactions between cancer cells and stromal cells in the tumor microenvironment (TME). The identification of cytotoxic tumor-infiltrating lymphocytes has instigated research into immune stimulating cancer therapies. Although a promising direction, immunosuppressive mechanisms exerted at the TME hamper its success. Myeloid-derived suppressor cells (MDSCs) have come to the forefront as stromal cells that orchestrate the immunosuppressive TME. Consequently, this heterogeneous cell population has been the object of investigation. Studies revealed that the transcription factor signal transducer and activator of transcription 3 (STAT3) largely dictates the recruitment, activation and function of MDSCs in the TME. Therefore, this review will focus on the role of this key transcription factor during the MDSC's life cycle and on the therapeutic opportunities it offers.

Keywords: MDSC; STAT3; T cell; immunotherapy; radiotherapy.

Publication types

  • Review

MeSH terms

  • Animals
  • Humans
  • Immunosuppression Therapy
  • Immunotherapy
  • Inflammation
  • Lymphocytes, Tumor-Infiltrating / immunology
  • Mice
  • Myeloid-Derived Suppressor Cells / metabolism*
  • Neoplasms / drug therapy*
  • Neoplasms / metabolism*
  • RNA Interference
  • Radiotherapy
  • STAT3 Transcription Factor / metabolism*
  • Signal Transduction
  • T-Lymphocytes / metabolism
  • Treatment Outcome
  • Tumor Microenvironment / immunology

Substances

  • STAT3 Transcription Factor
  • STAT3 protein, human