An activation to memory differentiation trajectory of tumor-infiltrating lymphocytes informs metastatic melanoma outcomes.
An activation to memory differentiation trajectory of tumor-infiltrating lymphocytes informs metastatic melanoma outcomes.
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肿瘤浸润性淋巴细胞的记忆分化激活轨迹提示转移性黑色素瘤的结果。
DOI：
10.1016/j.ccell.2022.04.005
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发表时间：
2022-05-09
期刊：
影响因子：
50.3
通讯作者：
Anandasabapathy, Niroshana
中科院分区：
文献类型：
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作者：
Jaiswal, Abhinav;Verma, Akanksha;Dannenfelser, Ruth;Melssen, Marit;Tirosh, Itay;Izar, Benjamin;Kim, Tae-Gyun;Nirschl, Christopher J.;Devi, K. Sanjana P.;Olson, Walter C., Jr.;Slingluff, Craig L., Jr.;Engelhard, Victor H.;Garraway, Levi;Regev, Aviv;Minkis, Kira;Yoon, Charles H.;Troyanskaya, Olga;Elemento, Olivier;Suarez-Farinas, Mayte;Anandasabapathy, Niroshana
需要更好地分类和理解肿瘤浸润淋巴细胞（TIL）。在这里，我们应用先进的功能基因组学来询问 9000 个人类肿瘤，以及使用基准 T 细胞状态、全面 T 细胞分化轨迹、人类和小鼠疫苗反应以及其他人类 TIL 的多个单细胞测序集。与其他 T 细胞状态相比，在实体瘤中观察到 T 记忆/驻留记忆程序的丰富。单细胞黑色素瘤 CD8+ TIL 的轨迹分析还发现，抗 PD-1 应答者中有很高比例的记忆/常驻记忆评分 TIL，且在治疗后会扩大。相比之下，TIL 在早期 T 细胞激活方面得分较高，但在与无反应相关的衰竭方面得分较低。晚期/持续而非早期的激活特征可预测黑色素瘤的存活，并与树突状细胞和 IFN-γ 反应程序共表达。这些数据确定了与不良反应相关的类激活状态，并表明成功的记忆转换（高于疲劳复苏）是成功抗肿瘤免疫的一个未被充分认识的方面。贾斯瓦尔等人。通过显示当前转录组分配可能将早期激活/效应 TIL 错误分类为耗尽，强调改进肿瘤浸润淋巴细胞 (TIL) 分类的必要性。该研究调查了 9000 个实体瘤、多个单细胞 RNA 测序集、小鼠和人类模型以及评分方法，以重新分类 TIL 并将黑色素瘤存活率与 T 细胞记忆/常驻记忆联系起来。
There is a need for better classification and understanding of tumor infiltrating lymphocytes (TILs). Here we applied advanced functional genomics to interrogate 9000 human tumors, and multiple single-cell sequencing sets using benchmarked T cell states, comprehensive T cell differentiation trajectories, human and mouse vaccine responses, and other human TILs. Compared to other T cell states, enrichment of T memory/resident memory programs was observed across solid tumors. Trajectory analysis of single-cell melanoma CD8+ TILs also identified a high fraction of memory/resident memory-scoring TILs in anti-PD-1 responders, which expanded post therapy. In contrast, TILs scoring highly for early T cell activation, but not exhaustion, associated with non-response. Late/persistent, but not early activation signatures, prognosticate melanoma survival, and co-express with dendritic cell and IFN-γ response programs. These data identify an activation-like state associated to poor response and suggest successful memory conversion, above resuscitation of exhaustion, is an under-appreciated aspect of successful anti-tumoral immunity. Jaiswal et al. highlight the need for improved tumor infiltrating lymphocyte (TIL) classification by showing current transcriptome assignments may misclassify early activated/effector TILs as exhausted. The study surveys 9000 solid tumors, multiple single-cell RNA sequencing sets, mouse and human models, and scoring methods to reclassify TILs and associate melanoma survival to T cell memory/resident memory.
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DOI：
10.4049/jimmunol.1602033
发表时间：
2017-10-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Brignall R;Cauchy P;Bevington SL;Gorman B;Pisco AO;Bagnall J;Boddington C;Rowe W;England H;Rich K;Schmidt L;Dyer NP;Travis MA;Ott S;Jackson DA;Cockerill PN;Paszek P
通讯作者：
Paszek P
影响因子：
4.3
作者：
Cavill R;Kamburov A;Ellis JK;Athersuch TJ;Blagrove MS;Herwig R;Ebbels TM;Keun HC
通讯作者：
Keun HC
影响因子：
15.9
作者：
Baitsch, Lukas;Baumgaertner, Petra;Speiser, Daniel E.
通讯作者：
Speiser, Daniel E.
影响因子：
4.4
作者：
Djenidi, Faycal;Adam, Julien;Mami-Chouaib, Fathia
通讯作者：
Mami-Chouaib, Fathia
影响因子：
64.8
作者：
Baeyens A;Bracero S;Chaluvadi VS;Khodadadi-Jamayran A;Cammer M;Schwab SR
通讯作者：
Schwab SR