Resident and circulating memory T cells persist for years in melanoma patients with durable responses to immunotherapy.
Resident and circulating memory T cells persist for years in melanoma patients with durable responses to immunotherapy.
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在对免疫治疗有持久反应的黑色素瘤患者中，常驻和循环记忆T细胞可持续存在数年。
DOI：
10.1038/s43018-021-00180-1
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发表时间：
2021-03
期刊：
影响因子：
22.7
通讯作者：
Angeles CV
中科院分区：
文献类型：
--
作者：
Han J;Zhao Y;Shirai K;Molodtsov A;Kolling FW;Fisher JL;Zhang P;Yan S;Searles TG;Bader JM;Gui J;Cheng C;Ernstoff MS;Turk MJ;Angeles CV
虽然T细胞对癌症免疫疗法的反应已经被大量研究，但长期记忆的特征却很差。在一组对免疫治疗有特殊反应的转移性黑色素瘤幸存者中，我们在几年内探索了组织中的记忆性CD 8 + T细胞反应。单细胞RNA测序揭示了肿瘤和远处白癜风影响的皮肤之间共享的三个常驻记忆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TRM共存，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，肿瘤的克隆型在患者皮肤和血液中发现长达9年，皮肤保持了最集中的肿瘤相关克隆库。这些研究表明，癌症幸存者可以保持持久的记忆功能，广泛分布的TRM和TEM隔间。
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 (TRM) cells shared between tumors and distant vitiligo-affected skin. Paired T-cell receptor sequencing further identified clonotypes in tumors that co-existed as TRM in skin and as effector memory T (TEM) cells in blood. Clonotypes that dispersed throughout tumor, skin, and blood preferentially expressed a IFNG / TNF-high signature, which had a strong prognostic value for melanoma patients. Remarkably, clonotypes from tumors were found in patient skin and blood up to nine 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 TRM and TEM compartments.
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影响因子：
82.9
作者：
Fairfax BP;Taylor CA;Watson RA;Nassiri I;Danielli S;Fang H;Mahé EA;Cooper R;Woodcock V;Traill Z;Al-Mossawi MH;Knight JC;Klenerman P;Payne M;Middleton MR
通讯作者：
Middleton MR
影响因子：
32.4
作者：
Herndler-Brandstetter D;Ishigame H;Shinnakasu R;Plajer V;Stecher C;Zhao J;Lietzenmayer M;Kroehling L;Takumi A;Kometani K;Inoue T;Kluger Y;Kaech SM;Kurosaki T;Okada T;Flavell RA
通讯作者：
Flavell RA
影响因子：
82.9
作者：
Gattinoni L;Lugli E;Ji Y;Pos Z;Paulos CM;Quigley MF;Almeida JR;Gostick E;Yu Z;Carpenito C;Wang E;Douek DC;Price DA;June CH;Marincola FM;Roederer M;Restifo NP
通讯作者：
Restifo NP
影响因子：
158.5
作者：
Larkin, J.;Chiarion-Sileni, V.;Wolchok, J. D.
通讯作者：
Wolchok, J. D.
影响因子：
10.9
作者：
Hua, Camille;Boussemart, Lise;Robert, Caroline
通讯作者：
Robert, Caroline