Hyperthermic intraperitoneal chemotherapy leads to an anticancer immune response via exposure of cell surface heat shock protein 90

Oncogene. 2016 Jan 14;35(2):261-8. doi: 10.1038/onc.2015.82. Epub 2015 Apr 13.

Abstract

The occurrence of peritoneal carcinomatosis is a major cause of treatment failure in colorectal cancer and is considered incurable. However, new therapeutic approaches have been proposed, including cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy (HIPEC). Although HIPEC has been effective in selected patients, it is not known how HIPEC prolongs a patient's lifespan. Here, we have demonstrated that HIPEC-treated tumor cells induce the activation of tumor-specific T cells and lead to vaccination against tumor cells in mice. We have established that this effect results from the HIPEC-mediated exposure of heat shock protein (HSP) 90 at the plasma membrane. Inhibition or blocking of HSP90, but not HSP70, prevented the HIPEC-mediated antitumoral vaccination. Our work raises the possibility that the HIPEC procedure not only kills tumor cells but also induces an efficient anticancer immune response, therefore opening new opportunities for cancer treatment.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cancer Vaccines / immunology
  • Cancer Vaccines / pharmacology*
  • Cell Line, Tumor
  • Cell Membrane / metabolism
  • Coculture Techniques
  • Combined Modality Therapy
  • Dendritic Cells / immunology
  • HSP90 Heat-Shock Proteins / genetics
  • HSP90 Heat-Shock Proteins / metabolism*
  • Humans
  • Hyperthermia, Induced / methods*
  • Mice, Inbred BALB C
  • Peritoneal Neoplasms / drug therapy
  • Peritoneal Neoplasms / immunology*
  • Peritoneal Neoplasms / therapy*
  • Xenograft Model Antitumor Assays

Substances

  • Cancer Vaccines
  • HSP90 Heat-Shock Proteins