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Review
. 2006 Apr;55(4):355-62.
doi: 10.1007/s00262-005-0081-y. Epub 2005 Sep 27.

Renewed interest in cancer immunotherapy with the tumor necrosis factor superfamily molecules

Koji Tamada  1 , Lieping Chen
Affiliations
Review

Renewed interest in cancer immunotherapy with the tumor necrosis factor superfamily molecules

Koji Tamada et al. Cancer Immunol Immunother. 2006 Apr.

Abstract

Molecules belonging to the Tumor Necrosis Factor (TNF) and TNF receptor superfamilies have explosively expanded through the era of genomics and bioinformatics. Biological investigations of these molecules have explored their potency as attractive targets for cancer therapy. Anti-tumor mechanisms mediated by TNF superfamily molecules (TNFSF) could be classified into direct actions onto tumor cells and indirect effects through immune or non-immune components of tumor-bearing host. In this review, we focus on TRAIL, CD40, 4-1BB (CD137), and LIGHT as promising molecules to mediate powerful and selective anti-tumor responses, and summarize their unique effector mechanisms. In addition, optimal approaches to manipulate these molecules for cancer therapy are also discussed. We try to provide an insight into a role of TNFSF in cancer therapeutics and highlight each of their potency to be an important player in anti-cancer strategies.

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Figures

Fig. 1
Fig. 1
Multi-cellular mechanisms of anti-tumor effects through 4-1BB signal. During generation of anti-tumor immunity, 4-1BB signaling is capable of targeting at least three immune cell components, T cells, dendritic cells (DC), and NK cells. 4-1BB signal directly activates tumor-specific T cells, while 4-1BB signal to DC and NK cells indirectly stimulate T cells through cytokines, cognate interaction, or other unknown mechanisms. T cell activation induced by 4-1BB signal confer them the ability to overcome T cell tolerance associated with tumor-bearing conditions, thus leaving secondary lymphoid organs to migrate into the tumor site and attack tumor cells
Fig. 2
Fig. 2
Dual functions of LIGHT for the activation of anti-tumor immunity. LIGHT over-expressed on tumor cells triggers LTβR signal in tumor stromal cells to stimulate chemokine production and adhesion molecule expression such as CCL21 and MAdCAM-1. These factors attract T cells into the tumor site where they receive LIGHT–HVEM costimulatory signal to be activated into anti-tumor effector T cells
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