165 IRRADIATION OF RENAL CELL CARINOMA IN MURINE XENOGRAFT ATTENUATES TUMOR GROWTH AND MODULATES ANTITUMOR IMMUNE RESPONSE

INTRODUCTION AND OBJECTIVES: Renal cell carcinoma (RCC) was historically considered a radio-resistant malignancy; however, a recent study demonstrated significant attenuation of tumor growth and histologic changes with irradiation of mice implanted with a human RCC cell line. Radiation is known to cause significant up regulation of immunogenic cell surface markers in many human cancers, but little is known about the immunologic effect of radiation therapy in RCC. We investigated the effect of high dose radiotherapy on the growth of tumors in RCC implanted mice and the resultant immunologic changes within the tumor microenvironment. METHODS: Nude mice were injected subcutaneously with Renca renal cell carcinoma cells. Once tumors reached 5 mm in diameter they were irradiated with a 12 Gy dose of ionizing radiation. A control group was not irradiated. The tumors were measured every 2 days and their volume was calculated. A second group of mice were treated in the same manner, except the subjects were sacrificed at either 3 or 7 days after irradiation or once the tumor reached 15 mm (endpoint [EP]). Flow cytometry was performed on the tumors from the second group to assess expression of the various immunologic markers below. RESULTS: Marked attenuation in tumor growth was noted in the first group of mice, as illustrated in the graph below. The table below summarizes the flow cytometry findings. CONCLUSIONS: High dose radiation is effective in attenuating the growth of RCC and causes significant intratumoral immunologic changes. Radiation decreased the T regulatory and increased cytotoxic T cell populations while increasing CD80, CD86 and MHC Class 1 expression on tumor cells. These intratumoral immunologic effects may lead to a tumor specific immune response following radiation of RCC.