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

Academic Article

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. © 2013 Elsevier Inc.
  • Digital Object Identifier (doi)

    Author List

  • Wada S; Harris TJ; Tryggestad E; Yoshimura K; Zeng J; Yen HR; Getnet D; Grosso JF; Bruno TC; De Marzo AM
  • Start Page

  • 769
  • End Page

  • 776
  • Volume

  • 87
  • Issue

  • 4