Induction of hsp70-mediated Th17 autoimmunity can be exploited as immunotherapy for metastatic prostate cancer

Timothy Kottke, Luis Sanchez-Perez, Rosa Maria Diaz, Jill Thompson, Heung Chong, Kevin Harrington, Stuart K. Calderwood, Jose Pulido, Nick Georgopoulos, Peter Selby, Alan Melcher, Richard Vile

Research output: Contribution to journalArticle

73 Scopus citations

Abstract

A close connectivity between autoimmune and tumor rejection responses is known to exist in the case of melanoma immunotherapy. However, relatively little is known about self-antigens on other types of normal cells, their relation to the development of autoimmune disease, and their possible coexistence as potential tumor rejection antigens on associated tumors. In the current study, we induced inflammatory killing of normal prostate tissue in situ using a fusogenic membrane glycoprotein along with the immune adjuvant hsp70. We show here that, in the prostate, hsp70 induces interleukin (IL)-6, which triggers a CD4- and CD8-dependent progressive autoimmune reactivity, associated with IL-17 expression. This autoimmune response was also able to induce the rejection of established prostate tumors, but not other histologic types of tumors, growing elsewhere in the animal. These data show that the intimate connectivity between autoimmune and tumor rejection responses extends beyond the classic melanoma paradigm and may be clinically valuable for the treatment of established metastatic disease of the prostate.

Original languageEnglish (US)
Pages (from-to)11970-11979
Number of pages10
JournalCancer research
Volume67
Issue number24
DOIs
StatePublished - Dec 15 2007

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Kottke, T., Sanchez-Perez, L., Diaz, R. M., Thompson, J., Chong, H., Harrington, K., Calderwood, S. K., Pulido, J., Georgopoulos, N., Selby, P., Melcher, A., & Vile, R. (2007). Induction of hsp70-mediated Th17 autoimmunity can be exploited as immunotherapy for metastatic prostate cancer. Cancer research, 67(24), 11970-11979. https://doi.org/10.1158/0008-5472.CAN-07-2259