小柯机器人

第三军医大学刘新东、卞修武等研究组合作发现中和IL-8增强免疫检查点阻断(ICB)对胶质瘤的疗效。相关论文于2023年3月23日发表在《癌细胞》杂志上。

为了探索潜在的免疫调节因子，他们检查了胶质瘤的微环境，发现肿瘤浸润的T细胞主要局限于血管周围袖口，并表达高水平的CCR5、CXCR3和程序性细胞死亡蛋白1 (PD-1)。结合T细胞聚类和T细胞受体(TCR)克隆扩增分析，潜在的肿瘤杀伤T细胞主要分为预耗尽/耗尽和效应CD8+ T亚群，以及细胞毒性CD4+ T亚群。值得注意的是，CD4+ T细胞的一个独特亚群表现出先天特征，优先表达白细胞介素-8 (IL-8)。

通过IL-8人源化小鼠毒株，他们证明产生IL-8的CD4+ T细胞、髓系细胞和肿瘤细胞协调骨髓来源的抑制细胞浸润和血管生成，这导致肿瘤生长增强，但降低了ICB的疗效。抗体介导的IL-8阻断或其受体CXCR1/2的抑制，释放抗PD -1介导的抗肿瘤免疫。因此，他们的研究结果强调IL-8是胶质瘤的联合免疫治疗靶点。

研究人员表示，恶性胶质瘤在很大程度上对ICB治疗难治。

附：英文原文

Title: Neutralizing IL-8 potentiates immune checkpoint blockade efficacy for glioma

Author: Haofei Liu, Qiwen Zhao, Leyong Tan, Xin Wu, Rui Huang, Yonglin Zuo, Longjuan Chen, Jigui Yang, Zuo-Xin Zhang, Wenchen Ruan, Jiayang Wu, Fei He, Yiliang Fang, Fangyuan Mao, Peipei Zhang, Xiaoning Zhang, Peidi Yin, Zexuan Yan, Wenwen Xu, Huimin Lu, Qingrui Li, Mei Liang, Yanjun Jia, Cong Chen, Senlin Xu, Yu Shi, Yi-Fang Ping, Guang-Jie Duan, Xiao-Hong Yao, Zhijian Han, Tao Pang, Youhong Cui, Xia Zhang, Bo Zhu, Chunjian Qi, Yan Wang, Sheng-Qing Lv, Xiu-Wu Bian, Xindong Liu

Issue&Volume: 2023-03-23

Abstract: Malignant gliomas are largely refractory to immune checkpoint blockade (ICB) therapy. To explore the underlying immune regulators, we examine the microenvironment in glioma and find that tumor-infiltrating T cells are mainly confined to the perivascular cuffs and express high levels of CCR5, CXCR3, and programmed cell death protein 1 (PD-1). Combined analysis of T cell clustering with T cell receptor (TCR) clone expansion shows that potential tumor-killing T cells are mainly categorized into pre-exhausted/exhausted and effector CD8+ T subsets, as well as cytotoxic CD4+ T subsets. Notably, a distinct subpopulation of CD4+ T cells exhibits innate-like features with preferential interleukin-8 (IL-8) expression. With IL-8-humanized mouse strain, we demonstrate that IL-8-producing CD4+ T, myeloid, and tumor cells orchestrate myeloid-derived suppressor cell infiltration and angiogenesis, which results in enhanced tumor growth but reduced ICB efficacy. Antibody-mediated IL-8 blockade or the inhibition of its receptor, CXCR1/2, unleashes anti-PD-1-mediated antitumor immunity. Our findings thus highlight IL-8 as a combinational immunotherapy target for glioma.

DOI: 10.1016/j.ccell.2023.03.004

Source: https://www.cell.com/cancer-cell/fulltext/S1535-6108(23)00077-6

Cancer Cell：《癌细胞》，创刊于2002年。隶属于细胞出版社，最新IF：38.585
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