Targeting of the Tumor Necrosis Factor Receptor Superfamily for Cancer Immunotherapy

The tumor necrosis factor (TNF) ligand and cognate TNF receptor superfamilies constitute an important regulatory axis that is pivotal for immune homeostasis and correct execution of immune responses. TNF ligands and receptors are involved in diverse biological processes ranging from the selective induction of cell death in potentially dangerous and superfluous cells to providing costimulatory signals that help mount an effective immune response. This diverse and important regulatory role in immunity has sparked great interest in the development of TNFL/TNFR-targeted cancer immunotherapeutics. In this review, I will discuss the biology of the most prominent proapoptotic and co-stimulatory TNF ligands and review their current status in cancer immunotherapy.