TNFR2: A Novel Target for Cancer Immunotherapy

Trends Mol Med. 2017 Nov;23(11):1037-1046. doi: 10.1016/j.molmed.2017.09.007. Epub 2017 Oct 12.


Immune checkpoint inhibitors (ICIs) have revolutionized cancer therapy but exhibit variable efficacy and relapse and can induce autoimmunity. Tumor necrosis factor (TNF) receptor 2 (TNFR2) is a signaling molecule found on the surface of a subset of potent regulatory T cells (Tregs) that can activate the proliferation of these cells through nuclear factor kappa B (NF-κB). TNFR2 is also abundantly expressed on the surface of many human tumors. We propose that blocking TNFR2 might target abundant TNFR2+ tumor-infiltrating Tregs and directly kill TNFR2-expressing tumors. We also posit that TNFR2 inhibitors might potentially constitute safer and more targeted alternatives to ICI cancer treatment because the expression of TNFR2 on immune cells, concentrated in the tumor microenvironment of various cancers, appears to be more selective than that of checkpoint molecules.

Keywords: TNFR2 antagonism; cancer; checkpoint inhibitors; immunotherapy; oncogene; regulatory T cells; tumor microenvironment.

Publication types

  • Review

MeSH terms

  • Animals
  • Humans
  • Immunotherapy / methods
  • NF-kappa B / immunology
  • Neoplasms / immunology*
  • Neoplasms / therapy*
  • Receptors, Tumor Necrosis Factor, Type II / immunology*
  • Signal Transduction / immunology
  • T-Lymphocytes, Regulatory / immunology
  • Tumor Microenvironment / immunology


  • NF-kappa B
  • Receptors, Tumor Necrosis Factor, Type II