Role of 4-1BB:4-1BB ligand in cancer immunotherapy

Cancer Gene Ther. 2004 Mar;11(3):215-26. doi: 10.1038/sj.cgt.7700670.


The activation of T cells plays a central role in antitumor immunity. In order to activate naïve T cells, two key signals are required. Signal one is provided through the T-cell receptor (TCR) while signal two is that of costimulation. The CD28:B7 molecules are one of the best-studied costimulatory pathways, thought to be the main mechanism through which primary T-cell stimulation occurs. However, a number of molecules have been identified which serve to amplify and diversify the T-cell response, following initial T-cell activation. These include the more recently described 4-1BB:4-1BB ligand (4-1BBL) molecules. 4-1BB:4-1BBL are a member of the TNFR:TNF ligand family, which are expressed on T cells and antigen-presenting cells (APCs), respectively. Therapies utilizing the 4-1BB:4-1BBL signaling pathway have been shown to have antitumor effects in a number of model systems. In this paper, we focus on the 4-1BB:4-1BBL costimulatory molecules. In particular, we will describe the structure and function of the 4-1BB molecule, its receptor and how 4-1BB:4-1BBL costimulation has and may be used for the immunotherapy of cancer.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • 4-1BB Ligand
  • Amino Acid Sequence
  • Animals
  • Antigens, CD
  • B7-1 Antigen / metabolism
  • B7-1 Antigen / therapeutic use
  • CD28 Antigens / metabolism
  • Cancer Vaccines / metabolism
  • Cancer Vaccines / therapeutic use
  • Clinical Trials as Topic
  • Disease Models, Animal
  • Humans
  • Mice
  • Molecular Sequence Data
  • Neoplasms / immunology
  • Neoplasms / therapy*
  • Receptors, Nerve Growth Factor / genetics
  • Receptors, Nerve Growth Factor / metabolism*
  • Receptors, Nerve Growth Factor / physiology
  • Receptors, Tumor Necrosis Factor / genetics
  • Receptors, Tumor Necrosis Factor / metabolism*
  • Receptors, Tumor Necrosis Factor / physiology
  • Signal Transduction / immunology
  • T-Lymphocytes / immunology
  • T-Lymphocytes / metabolism
  • Tumor Necrosis Factor Receptor Superfamily, Member 9
  • Tumor Necrosis Factor-alpha / genetics
  • Tumor Necrosis Factor-alpha / metabolism*
  • Tumor Necrosis Factor-alpha / physiology


  • 4-1BB Ligand
  • Antigens, CD
  • B7-1 Antigen
  • CD28 Antigens
  • Cancer Vaccines
  • Receptors, Nerve Growth Factor
  • Receptors, Tumor Necrosis Factor
  • TNFRSF9 protein, human
  • TNFSF9 protein, human
  • Tnfrsf9 protein, mouse
  • Tnfsf9 protein, mouse
  • Tumor Necrosis Factor Receptor Superfamily, Member 9
  • Tumor Necrosis Factor-alpha