Metastasis enables immunogenicity through migrasome-mediated antigen release

IF 26.5 1区医学 Q1 IMMUNOLOGY

Nature Immunology Pub Date : 2026-09-22 DOI:10.1038/s41590-026-02641-0

Dong Jiang, Jinzhao He, Renxiang Xie, Minghui Shi, Siyuan Liu, Haohao Jia, Bingjie Yang, Xiaojie Ruan, Xiaoyu Tao, Yuhan Xiang, Yining Chen, Lin Jiao, Xiaoyu Feng, Li Yu

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引用次数: 0

Abstract

Antigen release is a critical step in initiating antitumor immune responses, yet its regulation during metastasis is not well understood. Here we show that circulating tumor cells undergoing vascular migration produce migrasomes that serve as a metastasis-specific mechanism of antigen release. These migrasomes are enriched in tumor-associated antigens, including cancer-testis and mutated antigens, and are captured efficiently by antigen-presenting cells in secondary lymphoid organs, where they undergo cross-presentation to elicit CD8+ T cell-mediated immune responses that constrain metastatic progression. Genetic inhibition of migrasome formation enhances metastasis, while administration of purified cancer-derived migrasomes restores immune-mediated suppression of metastatic growth. These findings show paradoxically that metastasis can enhance tumor immunogenicity through migrasome-mediated antigen release, highlighting a link between cancer dissemination and immune activation and establishing migrasomes as a distinct and potent platform for endogenous tumor antigen delivery. Here the authors show that circulating tumor cells shed migrasomes that carry tumor antigens, which in turn can activate CD8+ T cells through cross-presentation to restrict metastasis.

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转移通过迁移体介导的抗原释放实现免疫原性

抗原释放是启动抗肿瘤免疫反应的关键步骤，但其在转移过程中的调控尚不清楚。在这里，我们发现循环肿瘤细胞在进行血管迁移时会产生迁移体，作为转移特异性的抗原释放机制。这些迁移体富含肿瘤相关抗原，包括癌睾丸和突变抗原，并被次级淋巴器官中的抗原呈递细胞有效捕获，在那里它们经过交叉呈递以引发CD8+ T细胞介导的免疫反应，从而抑制转移进展。遗传抑制偏头痛形成增强转移，而纯化的癌症来源的偏头痛恢复免疫介导的转移生长抑制。这些发现矛盾地表明，转移可以通过迁移小体介导的抗原释放增强肿瘤的免疫原性，突出了癌症传播与免疫激活之间的联系，并将迁移小体作为内源性肿瘤抗原递送的独特而有效的平台。在这里，作者表明循环肿瘤细胞脱落携带肿瘤抗原的迁移体，这反过来又可以通过交叉呈递激活CD8+ T细胞来限制转移。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Nature Immunology 医学-免疫学

CiteScore

40.00

自引率

2.30%

发文量

248

审稿时长

4-8 weeks

期刊介绍： Nature Immunology is a monthly journal that publishes the highest quality research in all areas of immunology. The editorial decisions are made by a team of full-time professional editors. The journal prioritizes work that provides translational and/or fundamental insight into the workings of the immune system. It covers a wide range of topics including innate immunity and inflammation, development, immune receptors, signaling and apoptosis, antigen presentation, gene regulation and recombination, cellular and systemic immunity, vaccines, immune tolerance, autoimmunity, tumor immunology, and microbial immunopathology. In addition to publishing significant original research, Nature Immunology also includes comments, News and Views, research highlights, matters arising from readers, and reviews of the literature. The journal serves as a major conduit of top-quality information for the immunology community.