Targeting regulatory T cells in tumors

FEBS J. 2016 Jul;283(14):2731-48. doi: 10.1111/febs.13656. Epub 2016 Mar 1.


Regulatory T (Treg ) cells play a crucial role in maintaining peripheral tolerance and preventing autoimmunity. However, they also represent a major barrier to effective antitumor immunity and immunotherapy. Consequently, there has been considerable interest in developing approaches that can selectively or preferentially target Treg cells in tumors, while not impacting their capacity to maintain peripheral immune homeostasis. In this review, we describe our current understanding of the mechanisms underlying the recruitment, expansion, and suppressive activity of tumor-associated Treg cells, and discuss the approaches used and the challenges encountered in the immunotherapeutic targeting of Treg cells. In addition, we summarize the primary clinical targets and some emerging data on exciting new potential Treg cell-restricted targets. We propose that discovering and understanding mechanisms that are preferentially used by Treg cells within the tumor microenvironment will lead to strategies that selectively target Treg cell-mediated suppression of antitumor immunity while maintaining peripheral immune tolerance.

Keywords: cancer immunotherapy; immune contexture; immunosuppression; regulatory T cells; tumor microenvironment.

Publication types

  • Review
  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology
  • Cell Membrane / immunology
  • Cytokines / biosynthesis
  • Cytotoxicity, Immunologic
  • Humans
  • Immunotherapy
  • Lymphocyte Depletion
  • Lymphocytes, Tumor-Infiltrating / immunology
  • Models, Immunological
  • Neoplasms / immunology*
  • Neoplasms / therapy*
  • Peripheral Tolerance
  • T-Lymphocytes, Regulatory / drug effects
  • T-Lymphocytes, Regulatory / immunology*
  • Tumor Microenvironment / immunology


  • Antineoplastic Agents
  • Cytokines