While T-cell responses to cancer immunotherapy have been avidly studied, long-lived memory has been poorly characterized. In a cohort of metastatic melanoma survivors with exceptional responses to immunotherapy, we probed memory CD8⁺ T-cell responses across tissues, and across several years. Single-cell RNA sequencing revealed three subsets of resident memory T (T_RM) cells shared between tumors and distant vitiligo-affected skin. Paired T-cell receptor sequencing further identified clonotypes in tumors that co-existed as T_RM in skin and as effector memory T (T_EM) cells in blood. Clonotypes that dispersed throughout tumor, skin and blood preferentially expressed an IFNG/TNF-high signature, which had a strong prognostic value for patients with melanoma. Remarkably, clonotypes from tumors were found in patient skin and blood up to 9 years later, with skin maintaining the most focused tumor-associated clonal repertoire. These studies reveal that cancer survivors can maintain durable memory as functional, broadly distributed T_RM and T_EM compartments.

虽然 T 细胞对癌症免疫疗法的反应已被广泛研究，但长期记忆的特征却很少。在一组对免疫治疗具有特殊反应的转移性黑色素瘤幸存者中，我们探讨了跨组织和数年的记忆 CD8 ^{+ T 细胞反应。}单细胞 RNA 测序揭示了肿瘤和远处受白癜风影响的皮肤之间共有三个常驻记忆 T (TRM) 细胞_亚群。配对 T 细胞受体测序进一步鉴定了肿瘤中的克隆型，这些克隆型在皮肤中作为 T _RM细胞和在血液中作为效应记忆 T ( _TEM ) 细胞共存。分散在肿瘤、皮肤和血液中的克隆型优先表达IFNG / TNF高信号，这对黑色素瘤患者具有很强的预后价值。值得注意的是，长达 9 年后，在患者皮肤和血液中发现了来自肿瘤的克隆型，其中皮肤保留了最集中的肿瘤相关克隆库。这些研究表明，癌症幸存者可以通过功能性、广泛分布的 T _RM和 T _EM区室来维持持久记忆。