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Abstract

Purpose: 

While stereotactic body radiotherapy (SBRT) can reduce tumor volumes in patients with metastatic renal cell carcinoma (mRCC), 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 patients with mRCC and analyze the immunological impact of high-dose radiation.

Experimental Design:

Human RCC cell lines were irradiated and evaluated for immunomodulation. In a single-arm feasibility study, patients with mRCC were treated with 15 Gray 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).

Results: 

RCC cells treated in vitro with radiation had increased TAA expression compared with 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.

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 with archived RCC tumors. Collectively, these studies provide evidence of immunomodulation following SBRT in mRCC.

​Author information

Singh AK1, Winslow TB2, Kermany MH3, Goritz V3, Heit L3, Miller A4, Hoffend NC3, Stein LC5, Kumaraswamy LK2, Warren GW6, Bshara W5, Odunsi K7,8,9, Matsuzaki J8, Abrams SI9, Schwaab T3,9, Muhitch JB10,9.

1 Department of Radiation Medicine, Roswell Park Cancer Institute, Buffalo, New York. jason.muhitch@roswellpark.org anurag.singh@roswellpark.org.

2 Department of Radiation Medicine, Roswell Park Cancer Institute, Buffalo, New York.

3 Department of Urology, Roswell Park Cancer Institute, Buffalo, New York.

4 Department of Biostatistics and Bioinformatics, Roswell Park Cancer Institute, Buffalo, New York.

5 Department of Pathology, Roswell Park Cancer Institute, Buffalo, New York.

6 Department of Radiation Oncology, Medical University of South Carolina, Charleston, South Carolina.

7 Department of Gynecologic Oncology, Roswell Park Cancer Institute, Buffalo, New York.

8 Center for Immunotherapy, Roswell Park Cancer Institute, Buffalo, New York.

9 Department of Immunology, Roswell Park Cancer Institute, Buffalo, New York.

10 Department of Urology, Roswell Park Cancer Institute, Buffalo, New York. jason.muhitch@roswellpark.org anurag.singh@roswellpark.org.