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Metastasis enables immunogenicity through migrasome-mediated antigen release
Dong Jiang1, Jinzhao He2, Renxiang Xie2
1Department of Cardiology, State Key Laboratory of Transvascular Implantation Devices, Heart Regeneration and Repair Key Laboratory of Zhejiang Province, Transvascular Implantation Devices Research Institute, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China. jiang-dong@zju.edu.cn.
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.