Cytokine and chemokine expression in tumors of mice receiving systemic therapy with IL-12.
Cytokine and chemokine expression in tumors of mice receiving systemic therapy with IL-12.
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DOI：
10.4049/jimmunol.156.2.693
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发表时间：
1996-01
影响因子：
4.4
通讯作者：
C. Tannenbaum;Nancy L. Wicker;D. Armstrong;R. Tubbs;J. Finke;R. Bukowski;T. Hamilton
中科院分区：
文献类型：
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作者：
C. Tannenbaum;Nancy L. Wicker;D. Armstrong;R. Tubbs;J. Finke;R. Bukowski;T. Hamilton
IL-12介导的抗肿瘤活性的细胞和分子机制已被检查。BALB/c小鼠皮下接种每天用IL-12治疗的RENCA或CT 26肿瘤显示出基本上完全的肿瘤消退，而未治疗的动物中的肿瘤进行性生长。对来自治疗与未治疗小鼠的肿瘤组织中的炎性基因表达的检查揭示了IFN-γ和IFN-γ诱导的CXC趋化因子IP-10的选择性表达。免疫组织学分析表明，治疗小鼠的肿瘤大量浸润CD 8 + T细胞和Mac-1+单核细胞。IL-12处理小鼠的肿瘤消退与裂解效应分子穿孔素和颗粒酶B的表达相关。这些发现支持了IL-12治疗的抗肿瘤功能取决于T细胞和/或NK细胞诱导的IFN-γ表达、IFN-γ诱导的趋化因子细胞因子表达介导的免疫应答的扩增以及募集的CD 8 + T细胞的溶细胞效应子功能的IL-12依赖性增强的假设。
The cellular and molecular mechanisms of IL-12-mediated anti-tumor activity have been examined. BALB/c mice bearing established s.c. RENCA or CT26 tumors that were treated daily with IL-12 showed essentially complete tumor regression while tumors in untreated animals grew progressively. Examination of inflammatory gene expression in tumor tissue from treated vs untreated mice revealed the selective expression of IFN-gamma and the IFN-gamma-inducible CXC chemokine IP-10. Immunohistologic analysis demonstrated that tumors from treated mice were heavily infiltrated with CD8+ T cells and Mac-1+ mononuclear cells. Tumor regression in IL-12-treated mice was associated with expression of the lytic effector molecules perforin and granzyme B. These findings support the hypothesis that the anti-tumor function of IL-12 treatment depends upon the induced expression of IFN-gamma by T cells and/or NK cells, the amplification of the immune response mediated by IFN-gamma-induced expression of chemoattractant cytokines, and the IL-12-dependent potentiation of the cytolytic effector function of recruited CD8+ T cells.