The TNFRs OX40, 4-1BB, and CD40 as targets for cancer immunotherapy

Curr Opin Immunol. 2013 Apr;25(2):230-7. doi: 10.1016/j.coi.2013.01.004. Epub 2013 Feb 14.


T cell-mediated rejection of tumors requires signals from the T cell receptor and co-stimulatory molecules to license effector functions of tumor-antigen specific T cells. There is also an array of immune suppressive mechanisms within the tumor microenvironment that can suppress anti-tumor immunity. The use of monoclonal antibodies to overcome this suppression and/or enhance tumor-antigen specific T cell responses has shown promise in clinical trials. In particular, targeting co-stimulatory members of the tumor necrosis factor receptor (TNFR) family with agonist Abs enhances T cell function, which has led to encouraging therapeutic results in cancer-bearing hosts. These encouraging data establish TNFRs as important targets for enhancing tumor-specific immune responses in mice and man. This review will focus on agonists that target the TNFRs OX40, 4-1BB, and CD40.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Review

MeSH terms

  • Animals
  • CD40 Antigens / immunology*
  • Humans
  • Immunotherapy*
  • Neoplasms / immunology*
  • Neoplasms / pathology
  • Neoplasms / therapy*
  • Receptors, OX40 / immunology*
  • T-Lymphocytes / immunology
  • Tumor Necrosis Factor Receptor Superfamily, Member 9 / immunology*


  • CD40 Antigens
  • Receptors, OX40
  • Tumor Necrosis Factor Receptor Superfamily, Member 9