Combined treatment effects of radiation and immunotherapy: Studies in an autochthonous prostate cancer model

Satoshi Wada, Timothy J. Harris, Erik Tryggestad, Kiyoshi Yoshimura, Jing Zeng, Hung Rong Yen, Derese Getnet, Joseph F. Grosso, Tullia C. Bruno, Angelo M. De Marzo, George J. Netto, Drew M. Pardoll, Theodore L. Deweese, John Wong, Charles G. Drake

Research output: Contribution to journalArticle

Abstract

Purpose: To optimize the combination of ionizing radiation and cellular immunotherapy using a preclinical autochthonous model of prostate cancer. Methods and Materials: Transgenic mice expressing a model antigen under a prostate-specific promoter were treated using a platform that integrates cone-beam CT imaging with 3-dimensional conformal therapy. Using this technology we investigated the immunologic and therapeutic effects of combining ionizing radiation with granulocyte/macrophage colony-stimulating factor-secreting cellular immunotherapy for prostate cancer in mice bearing autochthonous prostate tumors. Results: The combination of ionizing radiation and immunotherapy resulted in a significant decrease in pathologic tumor grade and gross tumor bulk that was not evident with either single-modality therapy. Furthermore, combinatorial therapy resulted in improved overall survival in a preventive metastasis model and in the setting of established micrometastases. Mechanistically, combined therapy resulted in an increase of the ratio of effector-to-regulatory T cells for both CD4 and CD8 tumor-infiltrating lymphocytes. Conclusions: Our preclinical model establishes a potential role for the use of combined radiation-immunotherapy in locally advanced prostate cancer, which warrants further exploration in a clinical setting.

Original languageEnglish (US)
Pages (from-to)769-776
Number of pages8
JournalInternational Journal of Radiation Oncology Biology Physics
Volume87
Issue number4
DOIs
StatePublished - Nov 15 2013

ASJC Scopus subject areas

  • Radiation
  • Oncology
  • Radiology Nuclear Medicine and imaging
  • Cancer Research

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