近日，美国德克萨斯大学西南医学中心教授Yang-Xin Fu及其课题组探明了用IL-10靶向肿瘤可以防止树突状细胞介导的CD8⁺ T细胞凋亡。 相关论文于2019年6月10日发表于国际学术期刊《Cancer Cell》杂志上。

课题组合成基于西妥昔单抗的IL-10融合蛋白(CmAb-(IL10)₂)，以延长其半衰期，并允许靶向肿瘤传递IL-10。结果显示CmAb-(IL10)₂具有较强的抗肿瘤作用，且毒性较低。此外，研究小组发现CmAb(IL10)₂防止树突细胞(DC)介导的CD8⁺肿瘤浸润淋巴细胞发生细胞凋亡的机制是通过调节IFN-γ的产生。结合免疫检查点阻断，CmAb-(IL10)₂可显著提高晚期肿瘤小鼠的抗肿瘤作用。他们的发现揭示了IL-10的DC调节作用，增强CD8⁺ T细胞介导的抗肿瘤免疫，并为改善癌症免疫治疗提供了一个潜在的策略。

研究人员表示，越来越多的证据表明，白细胞介素-10 (IL-10)，作为一种免疫抑制细胞因子，诱导抗肿瘤作用依赖于CD8⁺ T细胞。然而，IL-10的免疫抑制作用如何促进CD8⁺ T细胞介导的抗肿瘤免疫作用仍然待解。

附：英文原文

Title: Targeting Tumors with IL-10 Prevents Dendritic Cell-Mediated CD8+ T Cell Apoptosis

Author: Jian Qiao, Zhida Liu, Chunbo Dong, Yan Luan, Anli Zhang, Casey Moore, Kai Fu, Jianjian Peng, Yang Wang, Zhenhua Ren, Chuanhui Han, Ting Xu, Yang-Xin Fu

Issue&Volume: Jun 10, 2019 Volume 35Issue 6

Abstract: Increasing evidence demonstrates that interleukin-10 (IL-10), known as an immunosuppressive cytokine, induces antitumor effects depending on CD8 + T cells. However, it remains elusive how immunosuppressive effects of IL-10 contribute to CD8 + T cell-mediated antitumor immunity. We generated Cetuximab-based IL-10 fusion protein (CmAb-(IL10) 2) to prolong its half-life and allow tumor-targeted delivery of IL-10. Our results demonstrated potent antitumor effects of CmAb-(IL10) 2 with reduced toxicity. Moreover, we revealed a mechanism of CmAb-(IL10) 2 preventing dendritic cell (DC)-mediated CD8 + tumor-infiltrating lymphocyte apoptosis through regulating IFN-γ production. When combined with immune checkpoint blockade, CmAb-(IL10) 2 significantly improves antitumor effects in mice with advanced tumors. Our findings reveal a DC-regulating role of IL-10 to potentiate CD8 + T cell-mediated antitumor immunity and provide a potential strategy to improve cancer immunotherapy.

DOI: https://doi.org/10.1016/j.ccell.2019.05.005

Source: https://www.cell.com/cancer-cell/fulltext/S1535-6108(19)30243-0