肿瘤微环境
免疫系统
免疫疗法
癌症研究
转移
T细胞
医学
免疫学
癌症
内科学
作者
Zhenyu Luo,Mengshi Jiang,Ningtao Cheng,Xiaoqi Zhao,Huihui Liu,Sijie Wang,Qing Lin,Jiaxin Huang,Xuemeng Guo,Бо Лю,Xinyu Shan,Yichao Lu,Yingying Shi,Lihua Luo,You Jian
标识
DOI:10.1016/j.jconrel.2024.07.057
摘要
Immune checkpoint inhibitors (ICIs) exhibit compromised therapeutic efficacy in many patients with advanced cancers, particularly those with liver metastases. Much of this incapability can be ascribed as an irresponsiveness resulting from the "cold" hepatic tumor microenvironment that acts as T cell "traps" for which there currently lack countermeasures. We report a novel nanomedicine that converts the hepatic immune microenvironment to a "hot" phenotype by targeting hepatic macrophage-centric T cell elimination. Using the nanomedicine, composed of KIRA6 (an endothelium reticulum stress inhibitor), α-Tocopherol nanoemulsions, and anti-PD1 antibodies, we found its potency in murine models of orthotopic colorectal tumors and hepatic metastases, restoring immune responses and enhancing anti-tumor effects. A post-treatment scrutiny of the immune microenvironment landscape in the liver reveals repolarization of immunosuppressive hepatic macrophages, upregulation of Th1-like effector CD4
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