TNFR2: A Novel Target for Cancer Immunotherapy

Éva S Vanamee; Denise L Faustman

doi:10.1016/j.molmed.2017.09.007

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.

Authors

Éva S Vanamee¹, Denise L Faustman²

Affiliations

¹ Immunobiology Department, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02129, USA.
² Immunobiology Department, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02129, USA. Electronic address: faustman@helix.mgh.harvard.edu.

PMID: 29032004
DOI: 10.1016/j.molmed.2017.09.007

Abstract

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 (T_regs) 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 T_regs 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

Substances

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