巨噬细胞肿瘤嵌合外泌体积聚在淋巴结和肿瘤中，激活抗肿瘤免疫反应

尽管多种免疫治疗技术实现了有效的T细胞活化，但由于肿瘤微环境中的高度免疫抑制条件，效应T细胞仍然缺乏效率。受纳米级分泌囊泡（称为外泌体）作为治疗剂的最新进展的启发，以及研究表明循环癌细胞具有返回主要肿瘤部位的“归巢”能力，我们产生了巨噬细胞 - 肿瘤杂交细胞。我们将从肿瘤细胞中分离的细胞核引入活化的M1样巨噬细胞中，以产生嵌合外泌体（aMT-exos）。aMT-exos能够在异种移植小鼠的淋巴结和各种肿瘤中积累。他们以经典的抗原呈递细胞诱导的免疫刺激方式和独特的“直接外泌体相互作用”方式进入淋巴结并启动T细胞活化。aMT-exos对肿瘤部位也有很强的“归巢行为”，在那里它们改善了免疫抑制。它们有效地诱导肿瘤消退并延长淋巴瘤、乳腺癌和黑色素瘤癌症的原发小鼠模型的生存期。此外，当与抗程序性死亡1（a-PD1）治疗相结合时，aMT-exos能够延长转移性和术后肿瘤复发小鼠模型的生存期。这种免疫反应和肿瘤微环境的共同激活使AMT-exos能够有效地抑制原发性肿瘤，肿瘤转移和术后肿瘤复发，以进行个性化免疫治疗，这值得在临床环境中进一步探索。

Although multiple immunotherapeutic technologies have enabled effective T cell activation, effector T cells remain inefficient due to the highly immunosuppressive conditions in the tumor microenvironment. Inspired by the recent advances in nanoscale secreted vesicles (known as exosomes) as therapeutics, as well as studies showing that circulating cancer cells possess the "homing" ability to return to primary tumor sites, we generated macrophage-tumor hybrid cells. We introduced nuclei isolated from tumor cells into activated M1-like macrophages to generate chimeric exosomes (aMT-exos). aMT-exos can accumulate in lymph nodes and various tumors of xenograft mice. They enter lymph nodes and initiate T cell activation via both the classic antigen-presenting cell-induced immunostimulatory manner and the unique "direct exosome interaction" manner. aMT-exos also exhibit strong "homing behavior" towards tumor sites, where they alleviate immunosuppression. They effectively induce tumor regression and prolong survival in primary mouse models of lymphoma, breast cancer, and melanoma. Furthermore, when combined with anti-programmed death 1 (a-PD1) therapy, aMT-exos can prolong survival in mouse models of metastatic and postoperative tumor recurrence. This co-activation of immune response and tumor microenvironment enables aMT-exos to effectively suppress primary tumors, tumor metastasis, and postoperative tumor recurrence for personalized immunotherapy, which warrants further exploration in clinical settings.

搜集汇总

背景与挑战

背景概述

该数据集围绕巨噬细胞-肿瘤嵌合外泌体（aMT-exos）的研究展开，通过实验验证了这些外泌体在淋巴结和肿瘤中的积累能力，能够激活T细胞免疫反应并改善肿瘤微环境，从而有效抑制淋巴瘤、乳腺癌和黑色素瘤等多种癌症的原发性肿瘤、转移和术后复发。数据集包含481.45MB的118个文件，由王爽于2022年发布，支持国家重点研发计划项目'仿生纳米药物用于高转移性肿瘤的精准治疗'，为肿瘤免疫治疗领域提供了重要的实验数据资源。