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Tumor immunogenicity is determined by the mechanism of cell death via induction of heat shock protein expression

Nature Medicine volume 4, pages 581–587 (1998)Cite this article

Abstract

In situ killing of tumor cells using suicide gene transfer to generate death by a non-apoptotic pathway was associated with high immunogenicity and induction of heat shock protein (hsp) expression. In contrast, a syngeneic colorectal tumor line, CMT93, killed predominantly by apoptosis, showed low levels of hsp expression and less immunogenicity. When apoptosis was inhibited in CMT93 cells by overexpression of bcl-2, hsp was also induced. Furthermore, when cDNA encoding hsp70 was stably transfected into BT6 and CMT93 cells, its expression significantly enhanced the immunogenicity of both tumors. Increased levels of hsp, induced by non-apoptotic cell killing, may provide an immunostimulatory signal in vivo which helps break tolerance to tumor antigens. These findings have important implications for the development of novel anti-cancer therapies aimed at promoting patients' immune responses to their own tumors.

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Authors and Affiliations

  1. Imperial Cancer Research Fund Laboratory of Molecular Therapy, ICRF Oncology Unit, Imperial College of Science and Medicine, Hammersmith Hospital, DuCane Road, London, W12 0NN, UK

    Alan Melcher, Stephen Todryk, Nicola Hardwick & Richard G. Vile

  2. Glaxo Wellcome Research and Development, Medicines Research Centre, Gunels Wood Road, Stevenage, Hertfordshire, SG1 2NY, UK

    Martin Ford

  3. Millenium Pharmaceuticals Inc, 640 Memorial Drive, Cambridge, Massachusetts, 02139-4815, USA

    Michael Jacobson

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Melcher, A., Todryk, S., Hardwick, N. et al. Tumor immunogenicity is determined by the mechanism of cell death via induction of heat shock protein expression. Nat Med 4, 581–587 (1998). https://doi.org/10.1038/nm0598-581

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