<p>While stereotactic body radiation therapy (SBRT) can reduce tumor volumes in metastatic renal cell carcinoma (mRCC) patients, little is known regarding the immunomodulatory effects of high-dose radiation in the tumor microenvironment. The main objectives of this pilot study were to assess the safety and feasibility of nephrectomy following SBRT treatment of mRCC patients and analyze the immunological impact of high-dose radiation.</p> <br /><br />Experimental Design: Human RCC cell lines were irradiated and evaluated for immunomodulation. In a single-arm feasibility study, mRCC patients were treated with 15 Gray (Gy) SBRT at the primary lesion in a single fraction followed 4 weeks later by cytoreductive nephrectomy. RCC specimens were analyzed for tumor-associated antigen (TAA) expression and T cell infiltration. The trial has reached accrual (ClinicalTrials.gov identifier: NCT01892930).<br /><br />Results: RCC cells treated in vitro with radiation had increased TAA expression compared to untreated tumor cells. Fourteen patients received SBRT followed by surgery and treatment was well tolerated. SBRT-treated tumors had increased expression of the immunomodulatory molecule calreticulin and TAA (CA9, 5T4, NY-ESO-1, and MUC-1). Ki67(+) proliferating CD8(+) T cells and FOXP3(+) cells were increased in SBRT-treated patient specimens in tumors and at the tumor-stromal interface compared with archived patient specimens.<br /><br />Conclusions: It is feasible to perform nephrectomy following SBRT with acceptable toxicity. Following SBRT, patient RCC tumors have increased expression of calreticulin, TAA, as well as a higher percentage of proliferating T cells compared to archived RCC tumors. Collectively, these studies provide evidence of immunomodulation following SBRT in mRCC.
Clinical cancer research : an official journal of the American Association for Cancer Research. 2017 Jun 19 [Epub ahead of print]
Anurag K Singh, Timothy B Winslow, Mohammad Habiby Kermany, Vincent Goritz, Lilia Heit, Austin Miller, Nicholas C Hoffend, Leighton C Stein, Lalith Kumaraswamy, Graham W Warren, Wiam Bshara, Kunle Odunsi, Junko Matsuzaki, Scott I Abrams, Thomas Schwaab, Jason B Muhitch
Radiation Medicine, Rosewell Park Cancer Center., Roswell Park Cancer Institute., Urology, Roswell Park Cancer Institute., Bioinformatics & Biostatistics, Roswell Park Cancer Institute., Gene expression core, Roswell Park Cancer Institute., Radiation Oncology, Hollings Cancer Center Medical University of South Carolina., Department of Pathology, Roswell Park Cancer Institute., Immunology and Center for Immunotherapy, Roswell Park Cancer Institute., Gynecologic Oncology & Immunology, Roswell Park Cancer Institute., Department of Tumor Immunology, Roswell Park Cancer Institute., Department of Urology, Roswell Park., Urology and Immunology, Roswell Park Cancer Institute .