抗原特异性CD8+T细胞在肿瘤中的积聚是有效免疫治疗的前提，然而淋巴细胞转移的机制并不完全清楚。我们展示了，肿瘤关联淋巴管通过趋化因子CXCL12控制T细胞从肿瘤中退出，而肿瘤内部抗原的遭遇调控效应CD8+T细胞中CXCR4的表达。只有高亲和性抗原可以下调CXCR4的表达，上调CXCL12的假受体ACKR3，从而减少CXCL12的敏感性并促进T细胞的滞留。因此，多样化的功能性肿瘤特异性CD8+T细胞离开肿瘤，限制了可用于控制肿瘤的CD8+T细胞池。CXCR4抑制或淋巴特异性CXCL12的缺失可以增强T细胞的滞留并促进肿瘤控制。这些数据表明限制T细胞的离开可能是促进肿瘤内部T细胞数量和质量以及对免疫治疗反应的策略。©2023。该作者授权独家许可Springer Nature America，Inc.

Antigen-specific CD8+ T cell accumulation in tumors is a prerequisite for effective immunotherapy, and yet the mechanisms of lymphocyte transit are not well defined. Here we show that tumor-associated lymphatic vessels control T cell exit from tumors via the chemokine CXCL12, and intratumoral antigen encounter tunes CXCR4 expression by effector CD8+ T cells. Only high-affinity antigen downregulates CXCR4 and upregulates the CXCL12 decoy receptor, ACKR3, thereby reducing CXCL12 sensitivity and promoting T cell retention. A diverse repertoire of functional tumor-specific CD8+ T cells, therefore, exit the tumor, which limits the pool of CD8+ T cells available to exert tumor control. CXCR4 inhibition or loss of lymphatic-specific CXCL12 boosts T cell retention and enhances tumor control. These data indicate that strategies to limit T cell egress might be an approach to boost the quantity and quality of intratumoral T cells and thereby response to immunotherapy.© 2023. The Author(s), under exclusive licence to Springer Nature America, Inc.