Combined Treatment Effects of Radiation and Immunotherapy: Studies in an Autochthonous Prostate Cancer Model
| Autor: | Erik Tryggestad, Hung-Rong Yen, Angelo M. De Marzo, Derese Getnet, Timothy J. Harris, Theodore L. DeWeese, Joseph F. Grosso, Satoshi Wada, Drew M. Pardoll, John Wong, George J. Netto, Jing Zeng, Tullia C. Bruno, Charles G. Drake, Kiyoshi Yoshimura |
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| Rok vydání: | 2013 |
| Předmět: |
Male
Organs at Risk Cancer Research Adoptive cell transfer Pathology medicine.medical_specialty medicine.medical_treatment Urinary Bladder Mice Transgenic Adenocarcinoma Cancer Vaccines Immunotherapy Adoptive T-Lymphocytes Regulatory Article Ionizing radiation Mice Prostate cancer Lymphocytes Tumor-Infiltrating Antigen Antigens Neoplasm Prostate Cell Line Tumor medicine Animals Combined Modality Therapy Radiology Nuclear Medicine and imaging Radionuclide Imaging Radiation business.industry Prostatic Neoplasms Radiotherapy Dosage T-Lymphocytes Helper-Inducer Immunotherapy Cone-Beam Computed Tomography medicine.disease Adoptive Transfer Tumor Burden Hemagglutinins medicine.anatomical_structure Oncology Neoplasm Micrometastasis Cancer research Neoplasm Grading Radiotherapy Conformal business |
| Zdroj: | International Journal of Radiation Oncology*Biology*Physics. 87:769-776 |
| ISSN: | 0360-3016 |
| DOI: | 10.1016/j.ijrobp.2013.07.015 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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