TNF: A moonlighting protein at the interface between cancer and infection

Harald Hundsberger, Alexander Verin, Christoph Wiesner, Maren Pflüger, Alexander Dulebo, Wolfgang Schütt, Ignace Lasters, Daniela N. Männel, Albrecht Wendel, Rudolf Lucas

Research output: Contribution to journalReview articlepeer-review

35 Scopus citations


The remarkable ability of TNF, especially in combination with Interferon-gamma or melphalan, to inhibit the growth of malignant tumor cells is so far unmatched. Unfortunately, its high systemic toxicity and hepatotoxicity prevent its systemic use in cancer patients. An elegant manner to circumvent this problem is the isolated limb and liver perfusion for the treatment of melanoma, soft tissue sarcoma and liver tumors, respectively, although the latter method can lead to a reversible hepatotoxicity. In order to allow also the treatment of other cancers with TNF, new strategies have to be developed that aim at sensitizing tumor cells to TNF and at reducing its systemic and liver toxicity, without losing its antitumor efficiency. Moreover, the lectin-like domain of TNF, which is spatially distinct from the receptor binding sites, could be useful in reducing cancer treatment-related pulmonary edema formation. This review will discuss some recent developments in these areas, which can lead to a renewed interest in TNF for the systemic treatment of cancer.

Original languageEnglish (US)
Pages (from-to)5374-5386
Number of pages13
JournalFrontiers in Bioscience
Issue number14
StatePublished - May 1 2008


  • ATP
  • Edema
  • Hepatotoxicity
  • Lectin-like domain
  • Review
  • TNF receptor 2
  • Tumor necrosis factor

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)


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