The nature of the anti-tumor immune response changes as primary tumors progress and metastasize. We investigated the role of resident memory (Trm) and circulating memory (Tcirm) cells in anti-tumor responses at metastatic locations using a mouse model of melanoma-associated vitiligo. We found that the transcriptional characteristics of tumor-specific CD8⁺ T cells were defined by the tissue of occupancy. Parabiosis revealed that tumor-specific Trm and Tcirm compartments persisted throughout visceral organs, but Trm cells dominated lymph nodes (LNs). Single-cell RNA-sequencing profiles of Trm cells in LN and skin were distinct, and T cell clonotypes that occupied both tissues were overwhelmingly maintained as Trm in LNs. Whereas Tcirm cells prevented melanoma growth in the lungs, Trm afforded long-lived protection against melanoma seeding in LNs. Expanded Trm populations were also present in melanoma-involved LNs from patients, and their transcriptional signature predicted better survival. Thus, tumor-specific Trm cells persist in LNs, restricting metastatic cancer.

抗肿瘤免疫反应的性质随着原发性肿瘤的进展和转移而变化。我们使用黑色素瘤相关白癜风小鼠模型研究了常驻记忆 (Trm) 和循环记忆 (Tcirm) 细胞在转移部位抗肿瘤反应中的作用。我们发现肿瘤特异性 CD8 ⁺ T 细胞的转录特征是由占据的组织决定的。联体共生表明，肿瘤特异性 Trm 和 Tcirm 区室存在于整个内脏器官中，但 Trm 细胞主导淋巴结 (LN)。淋巴结和皮肤中 Trm 细胞的单细胞 RNA 测序谱是不同的，占据这两种组织的 T 细胞克隆型在淋巴结中绝大多数维持为 Trm。 Tcirm 细胞可以阻止黑色素瘤在肺部生长，而 Trm 细胞可以提供长期保护，防止黑色素瘤在淋巴结中播种。扩大的 Trm 群体也存在于患者的黑色素瘤相关淋巴结中，它们的转录特征预示着更好的生存。因此，肿瘤特异性 Trm 细胞持续存在于淋巴结中，限制转移性癌症。