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Dual-mechanism based CTLs infiltration enhancement initiated by Nano-sapper potentiates immunotherapy against immune-excluded tumors.
Nature Communications ( IF 14.7 ) Pub Date : 2020-01-30 , DOI: 10.1038/s41467-020-14425-7 Yukun Huang 1 , Yu Chen 1 , Songlei Zhou 1 , Liang Chen 1 , Jiahao Wang 1 , Yuanyuan Pei 1 , Minjun Xu 1 , Jingxian Feng 1 , Tianze Jiang 1 , Kaifan Liang 1 , Shanshan Liu 1 , Qingxiang Song 2 , Gan Jiang 2 , Xiao Gu 2 , Qian Zhang 2 , Xiaoling Gao 2 , Jun Chen 1, 3
Nature Communications ( IF 14.7 ) Pub Date : 2020-01-30 , DOI: 10.1038/s41467-020-14425-7 Yukun Huang 1 , Yu Chen 1 , Songlei Zhou 1 , Liang Chen 1 , Jiahao Wang 1 , Yuanyuan Pei 1 , Minjun Xu 1 , Jingxian Feng 1 , Tianze Jiang 1 , Kaifan Liang 1 , Shanshan Liu 1 , Qingxiang Song 2 , Gan Jiang 2 , Xiao Gu 2 , Qian Zhang 2 , Xiaoling Gao 2 , Jun Chen 1, 3
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The failure of immunotherapies in immune-excluded tumor (IET) is largely ascribed to the void of intratumoral cytotoxic T cells (CTLs). The major obstacles are the excessive stroma, defective vasculatures and the deficiency of signals recruiting CTLs. Here we report a dual-mechanism based CTLs infiltration enhancer, Nano-sapper, which can simultaneously reduce the physical obstacles in tumor microenvironment and recruiting CTLs to potentiate immunotherapy in IET. Nano-sapper consists a core that co-loaded with antifibrotic phosphates-modified α-mangostin and plasmid encoding immune-enhanced cytokine LIGHT. Through reversing the abnormal activated fibroblasts, decreasing collagen deposition, normalizing the intratumoral vasculatures, and in situ stimulating the lymphocyte-recruiting chemoattractants expression, Nano-sapper paves the road for the CTLs infiltration, induces the intratumoral tertiary lymphoid structures, thus reshapes tumor microenvironment and potentiates checkpoint inhibitor against IET. This study demonstrates that the combination of antifibrotic agent and immune-enhanced cytokine might represent a modality in promoting immunotherapy against IET.
中文翻译：
由Nano-sapper启动的基于双机制的CTL渗透增强可增强针对免疫排斥肿瘤的免疫治疗。
免疫排斥肿瘤（IET）中免疫疗法的失败很大程度上归因于肿瘤内细胞毒性T细胞（CTL）的缺失。主要障碍是基质过多，血管系统缺陷以及缺乏募集CTL的信号。在这里，我们报告基于双机制的CTLs渗透增强剂Nano-sapper，它可以同时减少肿瘤微环境中的物理障碍，并募集CTL以增强IET中的免疫治疗。Nano-sapper由一个核心组成，该核心与抗纤维化磷酸盐修饰的α-mangostin和编码免疫增强型细胞因子LIGHT的质粒共同装载。通过逆转异常激活的成纤维细胞，减少胶原蛋白沉积，使肿瘤内脉管系统正常化并原位刺激淋巴细胞招募趋化因子的表达，纳米囊泡剂为CTL的渗透铺平了道路，诱导了肿瘤内第三级淋巴样结构，从而重塑了肿瘤微环境并增强了针对IET的检查点抑制剂。这项研究表明，抗纤维化剂和免疫增强细胞因子的结合可能代表了一种促进针对IET的免疫疗法的方式。
更新日期：2020-01-31
中文翻译：
由Nano-sapper启动的基于双机制的CTL渗透增强可增强针对免疫排斥肿瘤的免疫治疗。
免疫排斥肿瘤（IET）中免疫疗法的失败很大程度上归因于肿瘤内细胞毒性T细胞（CTL）的缺失。主要障碍是基质过多，血管系统缺陷以及缺乏募集CTL的信号。在这里，我们报告基于双机制的CTLs渗透增强剂Nano-sapper，它可以同时减少肿瘤微环境中的物理障碍，并募集CTL以增强IET中的免疫治疗。Nano-sapper由一个核心组成，该核心与抗纤维化磷酸盐修饰的α-mangostin和编码免疫增强型细胞因子LIGHT的质粒共同装载。通过逆转异常激活的成纤维细胞，减少胶原蛋白沉积，使肿瘤内脉管系统正常化并原位刺激淋巴细胞招募趋化因子的表达，纳米囊泡剂为CTL的渗透铺平了道路，诱导了肿瘤内第三级淋巴样结构，从而重塑了肿瘤微环境并增强了针对IET的检查点抑制剂。这项研究表明，抗纤维化剂和免疫增强细胞因子的结合可能代表了一种促进针对IET的免疫疗法的方式。
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