LOCAL TUMOR-IRRADIATION AUGMENTS THE RESPONSE TO IL-2 THERAPY IN A MURINE RENAL ADENOCARCINOMA

被引:46
作者
YOUNES, E
HAAS, GP
DEZSO, B
ALI, E
MAUGHAN, RL
KUKURUGA, MA
MONTECILLO, E
PONTES, JE
HILLMAN, GG
机构
[1] WAYNE STATE UNIV,SCH MED,DEPT RADIAT ONCOL,DETROIT,MI 48201
[2] WAYNE STATE UNIV,SCH MED,DIV HEMATOL & ONCOL,DETROIT,MI 48201
[3] HARPER GRACE HOSP,DETROIT,MI 48201
关键词
D O I
10.1006/cimm.1995.1211
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
We have previously demonstrated that local tumor irradiation effectively enhanced the therapeutic effect of IL-2 therapy on pulmonary metastases from a murine renal adenocarcinoma, Renca. Irradiation with 300 rad to the left lung only, followed by systemic IL-2 therapy, results in increased tumor reduction in both lungs, suggesting that radiation enhances the systemic effect of immunotherapy. In this study, we show that irradiation of the tumor-bearing organ is essential for the combined effect of both modalities. This effect is radiation dose-dependent as increases in the radiation dosage result in greater tumor reduction in the irradiated field as well as systemically in nonirradiated fields when combined with immunotherapy. We find that irradiation has a direct inhibitory effect on Renca cell growth in vitro. Irradiation of Renca cells also causes an upregulation in H-2K(d) class I MHC antigen detectable at 300 rad and more pronounced with 800 rad. By in vivo selective depletion of lymphocyte subsets, we demonstrate the involvement of Lyt-2(+) and L3T4(+) T cell subsets and AsGM1(+) cells, including NK cells, in the antitumor effect mediated by tumor irradiation and IL-2 therapy. Immunohistochemistry studies, performed on lung sections, showed a significant infiltration of CD3(+) T cells and macrophages in the tumor nodules following treatment with tumor irradiation and IL-2 therapy. Our studies indicate that the mechanism of interaction between tumor irradiation and immunotherapy may include radiation-induced alterations in the tumor growth and antigenicity which may enhance or trigger an anti-tumor response elicited by IL-2 and mediated by T cells, AsGM1(+) cells, and macrophages. (C) 1995 Academic Press, Inc.
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页码:243 / 251
页数:9
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