颗粒酶
免疫学
促炎细胞因子
炎症
免疫系统
医学
CD8型
癌症免疫疗法
细胞毒性T细胞
免疫疗法
肿瘤微环境
T细胞
细胞因子
癌症
癌症研究
生物
穿孔素
内科学
体外
生物化学
出处
期刊:Cancer immunology research
[American Association for Cancer Research]
日期:2014-03-01
卷期号:2 (3): 194-199
被引量:198
标识
DOI:10.1158/2326-6066.cir-13-0214
摘要
Abstract Human cancer is characterized by deficits in antigen-specific immunity and intratumoral CD8+ T cells. On the other hand, inflammatory macrophages and mediators of chronic inflammation are highly prevalent in patients with late-stage cancer. Intratumoral T-cell deficiency and chronic inflammation have been linked independently to a poor prognosis in patients with cancer, and therapeutic approaches to overcome either pathology separately are in clinical testing. The anti-inflammatory cytokine interleukin (IL)-10 suppresses macrophage and proinflammatory Th17 T-cell responses by inhibiting the inflammatory cytokines IL-6 and IL-12/23. Corroborating the anti-inflammatory action of IL-10, deficiency in IL-10 leads to a stimulation of inflammatory responses and inflammatory bowel disease. The anti-inflammatory role of IL-10 fostered the assumption that IL-10 undermines the immune response to cancer. However, mice and humans deficient in IL-10 signaling develop tumors spontaneously and at high rates. Overexpression of IL-10 in models of human cancer or treatment with a pegylated IL-10 (PEG-IL-10) led to tumor rejection and long-lasting tumor immunity. IL-10 stimulates cytotoxicity of CD8+ T cells and the expression of IFN-γ in CD8+ T cells. IL-10–induced tumor rejections are dependent on the expression of IFN-γ and granzymes in tumor-resident CD8+ T cells and the upregulation of MHC molecules. These findings reconcile earlier clinical data, which showed that recombinant IL-10 increased IFN-γ and granzymes in the blood of treated individuals. PEG-IL-10 is therefore a unique therapeutic agent, which simultaneously stimulates antitumor immunity and inhibits tumor-associated inflammation. Cancer Immunol Res; 2(3); 194–9. ©2014 AACR.
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