The role of TNF in cancer.

Tumor necrosis factor (TNF) is an extraordinarily pleiotropic cytokine with a central role in immune homeostasis, inflammation, and host defense. Dependent on the cellular context, it can induce such diverse effects as apoptosis, necrosis, angiogenesis, immune cell activation, differentiation, and cell migration. These processes are of great relevance in tumor immune surveillance, and also play crucial roles in tumor development and tumor progression. It is therefore no surprise that TNF in a context-dependent manner displays pro- and antitumoral effects. Modulation of the activity of the TNF-TNF receptor system thus offers manifold possibilities for cancer therapy. In fact, TNF in combination with melphalan is already an established treatment option in the therapy of advanced soft tissue sarcoma of the extremities and many preclinical data suggest that TNF neutralization could also be exploited to fight cancer or cancer-associated complications.