Geospatial immune variability illuminates differential evolution of lung adenocarcinoma.
Geospatial immune variability illuminates differential evolution of lung adenocarcinoma.
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DOI：
10.1038/s41591-020-0900-x
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发表时间：
2020-07
期刊：
影响因子：
82.9
通讯作者：
Yuan Y
中科院分区：
文献类型：
--
作者：
AbdulJabbar K;Raza SEA;Rosenthal R;Jamal-Hanjani M;Veeriah S;Akarca A;Lund T;Moore DA;Salgado R;Al Bakir M;Zapata L;Hiley CT;Officer L;Sereno M;Smith CR;Loi S;Hackshaw A;Marafioti T;Quezada SA;McGranahan N;Le Quesne J;TRACERx Consortium;Swanton C;Yuan Y
分子分析的显著进步提高了我们对癌细胞向免疫逃逸进化的理解。然而，免疫细胞和基质细胞的空间构型仍未得到解决，这可能有助于揭示跨越肿瘤地理位置的免疫逃逸的进化。我们将多区域外显子组和RNA-seq数据与深度学习绘制的空间组织学图结合在一起，研究了100名非小细胞肺癌(NSCLC)患者，这些患者来自跟踪癌症治疗进展(TRACERx)队列。来自免疫冷区的癌症亚克隆与来自免疫热区的亚克隆相比，在突变空间上具有更密切的亲缘关系。在TRACERx和由970名肺腺癌(LUAD)患者组成的独立多样本队列中，免疫冷区的数量与复发风险显著相关，与肿瘤大小、分期和每名患者的样本数量无关。在LUAD中，而不是肺鳞状细胞癌(LUSC)中，肿瘤区域癌细胞-基质细胞界面的几何不规则性和复杂性显著增加，而不破坏抗原递呈。在克隆性新抗原负荷较低的肿瘤中，可观察到邻近间质中淋巴细胞聚集减少。总的来说，免疫地理空间变异性阐明了肿瘤生态限制因素，这些限制因素可能影响免疫逃避亚克隆和侵袭性临床表型的出现。
Remarkable progress in molecular analyses has improved our understanding of the evolution of cancer cells towards immune escape. However, the spatial configurations of immune and stromal cells, which may shed light on the evolution of immune escape across tumor geographical locations, remain unaddressed. We integrated multi-region exome and RNA-seq data with spatial histology mapped by deep learning in 100 non-small cell lung cancer (NSCLC) patients from the TRAcking Cancer Evolution through Therapy (Rx) (TRACERx) cohort. Cancer subclones derived from immune cold regions were more closely related in mutation space, diversifying more recently than subclones from immune hot regions. In TRACERx and in an independent multi-sample cohort of 970 lung adenocarcinoma (LUAD) patients, the number of immune cold regions significantly correlated with risk of relapse, independently of tumor size, stage and number of samples per patient. In LUAD, but not lung squamous cell carcinoma (LUSC), geometrical irregularity and complexity of the cancer-stromal cell interface significantly increased in tumor regions without disruption of antigen presentation. Decreased lymphocyte accumulation in adjacent stroma was observed in tumors with low clonal neoantigen burden. Collectively, immune geospatial variability elucidates tumor ecological constraints that may shape the emergence of immune evading subclones and aggressive clinical phenotypes.
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影响因子：
64.5
作者：
Goltsev Y;Samusik N;Kennedy-Darling J;Bhate S;Hale M;Vazquez G;Black S;Nolan GP
通讯作者：
Nolan GP
影响因子：
--
作者：
Holzinger, A;Dingle, S;Whitsett, JA
通讯作者：
Whitsett, JA
影响因子：
48
作者：
Giesen, Charlotte;Wang, Hao A. O.;Bodenmiller, Bernd
通讯作者：
Bodenmiller, Bernd
影响因子：
2.9
作者：
DUBUC, B;QUINIOU, JF;ZUCKER, SW
通讯作者：
ZUCKER, SW
DOI：
10.1126/science.aaf1490
发表时间：
2016-03-25
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
McGranahan N;Furness AJ;Rosenthal R;Ramskov S;Lyngaa R;Saini SK;Jamal-Hanjani M;Wilson GA;Birkbak NJ;Hiley CT;Watkins TB;Shafi S;Murugaesu N;Mitter R;Akarca AU;Linares J;Marafioti T;Henry JY;Van Allen EM;Miao D;Schilling B;Schadendorf D;Garraway LA;Makarov V;Rizvi NA;Snyder A;Hellmann MD;Merghoub T;Wolchok JD;Shukla SA;Wu CJ;Peggs KS;Chan TA;Hadrup SR;Quezada SA;Swanton C
通讯作者：
Swanton C