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Immune regulation and cytotoxic T cell activation of IL-10 agonists - Preclinical and clinical experience.
Seminars in Immunology ( IF 7.4 ) Pub Date : 2019-11-06 , DOI: 10.1016/j.smim.2019.101325
Martin Oft 1
Affiliation  

The expansion and activation of tumor antigen reactive CD8+ T cells are primary goals of immunotherapies for cancer. IL-10 is an anti-inflammatory cytokine with an essential role in the development and proliferation of regulatory T cells, restricting myeloid and chronic inflammatory T cell responses. However, IL-10 is also essential for the expansion of antigen activated, tumor specific CD8+ T cells, leading to spontaneous tumor development in IL-10 deficient patients and mice. IL-10 induces IFNγ and cytotoxic mediators in antigen activated T cells. In clinical trials, monotherapy with recombinant, pegylated IL-10 (Pegilodecakin) induced objective responses in cancer patients. Patients receiving pegilodecakin had a systemic increase of IFNγ and granzymes, proliferation and expansion of immune checkpoint positive CD8+ T cells. Combination of pegilodecakin with anti-PD-1 appeared to improve on the efficacy of the single agents.



中文翻译:

IL-10 激动剂的免疫调节和细胞毒性 T 细胞激活 - 临床前和临床经验。

肿瘤抗原反应性 CD8 + T 细胞的扩增和激活是癌症免疫疗法的主要目标。IL-10 是一种抗炎细胞因子,在调节性 T 细胞的发育和增殖中具有重要作用,可限制骨髓和慢性炎症性 T 细胞反应。然而,IL-10 对于抗原激活的肿瘤特异性 CD8 +的扩增也是必不可少的T 细胞,导致 IL-10 缺陷患者和小鼠的自发肿瘤发展。IL-10 在抗原激活的 T 细胞中诱导 IFNγ 和细胞毒性介质。在临床试验中,重组聚乙二醇化 IL-10 (Pegilodecakin) 的单一疗法在癌症患者中诱导了客观反应。接受 pegilodecakin 治疗的患者全身性 IFNγ 和颗粒酶增加,免疫检查点阳性 CD8 + T 细胞增殖和扩增。pegilodecakin 与抗 PD-1 的组合似乎提高了单一药物的疗效。

更新日期:2019-11-06
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