免疫疗法
癌症免疫疗法
癌症
医学
抗原呈递
免疫检查点
CD8型
抗原
癌症疫苗
黑色素瘤
T细胞
免疫系统
肿瘤抗原
癌症研究
免疫学
内科学
作者
Gongxi Qiao,Shenglin Li,Xuefeng Pan,Peng Xie,Rong Peng,Xianghu Huang,Mengyun He,Jian‐Hui Jiang,Xia Chu
出处
期刊:Science Advances
[American Association for the Advancement of Science (AAAS)]
日期:2024-03-29
卷期号:10 (13)
标识
DOI:10.1126/sciadv.adk7955
摘要
Directly activating CD8+ T cells within the tumor through antigen-presenting cells (APCs) hold promise for tumor elimination. However, M2-like tumor-associated macrophages (TAMs), the most abundant APCs in tumors, hinder CD8+ T cell activation due to inefficient antigen cross-presentation. Here, we demonstrated a personalized nanotherapeutic platform using surgical tumor-derived galactose ligand-modified cancer cell membrane (CM)-coated cysteine protease inhibitor (E64)-loaded mesoporous silica nanoparticles for postsurgical cancer immunotherapy. The platform targeted M2-like TAMs and released E64 within lysosomes, which reshaped antigen cross-presentation and directly activated CD8+ T cells, thus suppressing B16-OVA melanoma growth. Furthermore, this platform, in combination with anti-PD-L1 antibodies, enhanced the therapeutic efficacy and substantially inhibited 4T1 tumor growth. CMs obtained from surgically resected tumors were used to construct a personalized nanotherapeutic platform, which, in synergy with immune checkpoint blockade (ICB), effectively inhibited postsurgical tumor recurrence in 4T1 tumor. Our work offered a robust, safe strategy for cancer immunotherapy and prevention of postsurgical tumor recurrence.
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