Androgen ablation mitigates tolerance to a prostate/prostate cancer-restricted antigen

Charles G. Drake, Amy D.H. Doody, Marianne A. Mihalyo, Ching Tai Huang, Erin Kelleher, Sowmya Ravi, Edward L. Hipkiss, Dallas B. Flies, Eugene P. Kennedy, Meixiao Long, Patrick W. McGary, Lee Coryell, William G. Nelson, Drew M. Pardoll, Adam J. Adler

Research output: Contribution to journalArticlepeer-review

215 Scopus citations

Abstract

To understand the T cell response to prostate cancer, we created transgenic mice that express a model antigen in a prostate-restricted pattern and crossed these animals to TRAMP mice that develop spontaneous prostate cancer. Adoptive transfer of prostate-specific CD4 T cells shows that, in the absence of prostate cancer, the prostate gland is mostly ignored. Tumorigenesis allows T cell recognition of the prostate gland - but this recognition is tolerogenic, resulting in abortive proliferation and ultimately in hyporesponsiveness at the systemic level. Androgen ablation (the most common treatment for metastatic prostate cancer) was able to mitigate this tolerance - allowing prostate-specific T cells to expand and develop effector function after vaccination. These results suggest that immunotherapy for prostate cancer may be most efficacious when administered after androgen ablation.

Original languageEnglish (US)
Pages (from-to)239-249
Number of pages11
JournalCancer cell
Volume7
Issue number3
DOIs
StatePublished - Mar 2005

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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