Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • News & Views
  • Published:

Burning up TNF toxicity for cancer therapy

The tumor-killing capacity and the systemic toxicity of the cytokine tumor necrosis factor (TNF) have appeared inseparable. Now a study shows that TNF loses its toxicity but still kills tumors in heat-treated mice.

This is a preview of subscription content, access via your institution

Access options

Rent or buy this article

Prices vary by article type

from$1.95

to$39.95

Prices may be subject to local taxes which are calculated during checkout

Figure 1: The TNF slot machine and heat shock:

References

  1. Coley, W.B. The treatment of malignant tumors by repeated inoculations of erysipelas; with a report of ten original cases. Am. J. Med. Sci. 105, 487–511 (1893).

    Article  Google Scholar 

  2. Carswell, E.A. et al. An endotoxin-induced serum factor that causes necrosis of tumors. Proc. Natl. Acad. Sci. USA 72, 3666–3670 (1975).

    Article  CAS  Google Scholar 

  3. Beutler, B. & Cerami, A. Cachectin and tumour necrosis factor as two sides of the same biological coin. Nature 320, 584–588 (1986).

    Article  CAS  Google Scholar 

  4. Fraker, D.L. & Alexander, H.R. Isolated limb perfusion with high-dose tumor necrosis factor for extremity melanoma and sarcoma. Important Adv. Oncol. 179–192 (1994).

  5. Van Molle, W. et al. HSP70 protects against TNF-induced lethal inflammatory shock. Immunity 16, 685–695 (2002).

    Article  CAS  Google Scholar 

  6. Jäättelä, M. Heat shock proteins as cellular lifeguards. Ann. Med. 31, 261–271 (1999).

    Article  Google Scholar 

  7. Jäättelä, M., Wissing, D., Bauer, P.A. & Li, G.C. Major heat shock protein hsp70 protects tumor cells from tumor necrosis factor cytotoxicity. EMBO J. 11, 3507–3512 (1992).

    Article  Google Scholar 

  8. Renard, N. et al. Early endothelium activation and polymorphonuclear cell invasion precede specific necrosis of human melanoma and sarcoma treated by intravascular high-dose tumour necrosis factor α (rTNFα). Int. J. Cancer 57, 656–663 (1994).

    Article  CAS  Google Scholar 

  9. Ruegg, C. et al. Evidence for the involvement of endothelial cell integrin αVβ3 in the disruption of the tumor vasculature induced by TNF and IFN-γ. Nature Med. 4, 408–414 (1998).

    Article  CAS  Google Scholar 

  10. Multhoff, G. et al. Heat shock protein 72 on tumor cells: A recognition structure for natural killer cells. J. Immunol. 158, 4341–4350 (1997).

    CAS  PubMed  Google Scholar 

  11. Blachere, N.E. et al. Heat shock protein-peptide complexes, reconstituted in vitro, elicit peptide-specific cytotoxic T lymphocyte response and tumor immunity. J. Exp. Med. 186, 1315–1322 (1997).

    Article  CAS  Google Scholar 

  12. Nylandsted, J. et al. Selective depletion of heat shock protein 70 (Hsp70) activates a tumor- specific death program that is independent of caspases and bypasses Bcl- 2. Proc. Natl. Acad. Sci. USA 97, 7871–7876 (2000).

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Leist, M., Jäättelä, M. Burning up TNF toxicity for cancer therapy. Nat Med 8, 667–668 (2002). https://doi.org/10.1038/nm0702-667

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1038/nm0702-667

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing