Clinical Cancer Research, Vol 2, Issue 9 1543-1552, Copyright © 1996 by American Association for Cancer Research

ARTICLES

The mechanism of local tumor irradiation combined with interleukin 2 therapy in murine renal carcinoma: histological evaluation of pulmonary metastases

B Dezso, GP Haas, F Hamzavi, S Kim, EJ Montecillo, PD Benson, JE Pontes, RL Maughan and GG Hillman
Department of Urology, Wayne State University School of Medicine and Harper Hospital, Detroit, Michigan 48201, USA.

We have demonstrated that tumor irradiation enhanced the therapeutic effect of interleukin 2 (IL-2) on pulmonary metastases from a murine renal adenocarcinoma, Renca. To investigate the mechanism of interaction between tumor irradiation and IL-2 therapy, we have histologically evaluated the effects of each therapy alone or in combination on Renca pulmonary metastases. Following treatment of established lung metastases with irradiation and IL-2 therapy, lung sections were processed for H&E or immunohistochemical staining. We found that tumor irradiation or IL-2 therapy locally induced vascular damage, resulting in multifocal hemorrhages and mononuclear cell mobilization in the lung tissue. This effect was amplified in lungs treated with the combined therapy. Immunohistochemistry showed that irradiation produced a macrophage influx into irradiated tumor nodules, and systemic IL-2 therapy induced T-cell infiltration in tumor nodules. Lungs treated with the combined therapy exhibited massive macrophage, T-cell, and natural killer cell mobilization in disintegrating tumor nodules and in the lung tissue. This combined therapy caused a decrease in the number of proliferating tumor cells and an increase in the number of apoptotic cells, which were more marked than with either therapy alone. We suggest that the macrophages mobilized by radiation-induced tissue injury could play a role in phagocytosis of apoptotic tumor cells, processing and presenting of tumor antigens for a systemic immune response activated by IL-2. Tumor destruction may result from the concomitant action of activated T cells, natural killer cells, and macrophages infiltrating the tumor nodules.

This article has been cited by other articles:

				J. Xian, H. Yang, Y. Lin, and S. Liu Combination Nonviral Murine Interleukin 2 and Interleukin 12 Gene Therapy and Radiotherapy for Head and Neck Squamous Cell Carcinoma Arch Otolaryngol Head Neck Surg, December 1, 2005; 131(12): 1079 - 1085. [Abstract] [Full Text] [PDF]

				A. A. Lugade, J. P. Moran, S. A. Gerber, R. C. Rose, J. G. Frelinger, and E. M. Lord Local Radiation Therapy of B16 Melanoma Tumors Increases the Generation of Tumor Antigen-Specific Effector Cells That Traffic to the Tumor J. Immunol., June 15, 2005; 174(12): 7516 - 7523. [Abstract] [Full Text] [PDF]

				D. Bray, S.-Z. Yu, H. Koprowski II, J. Rhee, S. Kumar, F. Pericle, M. Suntharalingam, D. A. Van Echo, D. Li, and B. W. O'Malley Jr Combination Nonviral Interleukin 2 Gene Therapy and External-Beam Radiation Therapy for Head and Neck Cancer Arch Otolaryngol Head Neck Surg, June 1, 2003; 129(6): 618 - 622. [Abstract] [Full Text] [PDF]

				G. G. Hillman, R. L. Maughan, D. J. Grignon, M. Yudelev, J. Rubio, S. Tekyi-Mensah, A. Layer, M. Che, and J. D. Forman Neutron or Photon Irradiation for Prostate Tumors: Enhancement of Cytokine Therapy in a Metastatic Tumor Model Clin. Cancer Res., January 1, 2001; 7(1): 136 - 144. [Abstract] [Full Text]