| 著者 |
Xing Y, Zhou Y, Wang R, Chen J, Yang L, Meng X, Wang J, Ouyang Q, Zhao J, Chen F, Saw PE, Fan J, Huang JD, Wu W, Liu Q, Song E, Huang D.
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| Abstract |
Tumor-antigen-specific CD8+ T cells (CTLs) are the main effector immunocytes in anti-tumor immunity, but their systemic deployment against cancer metastasis remains uncharacterized. Here, we found that the abundance of tumor-specific CD103+CD8+ T cells in the tumor-draining lymph nodes (TDLNs) was associated with improved lung-metastasis-free survival in breast cancer patients. In mouse cancer models, CD103+CD8+ T cells were primed in TDLNs and recruited to the lungs via C-C motif chemokine ligand 5/receptor 9 (CCL25/CCR9) signaling to inhibit metastasis through antigen-specific immunity. Furthermore, extracellular vesicles (EVs) from early- and late-stage tumors differentially polarized alveolar macrophages to release CCL25 and IDO1, respectively, and the latter impaired pulmonary CD103+CD8+ T cell deployment, facilitating lung metastasis. Depleting IDO1 effectively rescued CD103+CD8+ T cell-mediated protection against lung metastasis. These findings exemplified long-range deployment of adaptive immunity to protect distant organs from metastasis, highlighting the therapeutic potential of reconstituting effector immune cell deployment (EICD) for cancer treatment.
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