Signatures of plasticity, metastasis, and immunosuppression in an atlas of human small cell lung cancer.
Signatures of plasticity, metastasis, and immunosuppression in an atlas of human small cell lung cancer.
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DOI：
10.1016/j.ccell.2021.09.008
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发表时间：
2021-11-08
期刊：
影响因子：
50.3
通讯作者：
Rudin CM
中科院分区：
文献类型：
--
作者：
Chan JM;Quintanal-Villalonga Á;Gao VR;Xie Y;Allaj V;Chaudhary O;Masilionis I;Egger J;Chow A;Walle T;Mattar M;Yarlagadda DVK;Wang JL;Uddin F;Offin M;Ciampricotti M;Qeriqi B;Bahr A;de Stanchina E;Bhanot UK;Lai WV;Bott MJ;Jones DR;Ruiz A;Baine MK;Li Y;Rekhtman N;Poirier JT;Nawy T;Sen T;Mazutis L;Hollmann TJ;Pe'er D;Rudin CM
小细胞肺癌（SCLC）是一种侵袭性恶性肿瘤，包括由ASCL1、NEUROD1和POU2F3（分别为SCLC- a、-N和-P）的差异表达定义的亚型。为了确定肿瘤及其相关微环境在不同亚型之间的异质性，我们对来自21个人类生物标本的155,098个转录组进行了测序，其中包括54,523个SCLC转录组。我们观察到SCLC比肺腺癌更大的肿瘤多样性，由典型、中间和混合亚型驱动。我们发现一种plcg2高的SCLC表型具有茎样、促转移的特征，这种特征在不同亚型中反复出现，预示着更差的总生存率。SCLC比肺腺癌表现出更大的免疫隔离和更少的免疫浸润，SCLC- n比SCLC- a表现出更少的免疫浸润和更大的t细胞功能障碍。我们在SCLC肿瘤中发现了一个纤维化、免疫抑制的单核细胞/巨噬细胞群体，它与复发、plcg2高亚群特别相关。Chan等人利用单细胞转录组测序和成像技术研究临床小细胞肺癌标本的异质性和肿瘤微环境。该分析确定了与转移和预后不良相关的plcg2高表达亚群，以及具有纤维化，免疫抑制表型的单核细胞/巨噬细胞群的富集。
Small cell lung cancer (SCLC) is an aggressive malignancy that includes subtypes defined by differential expression of ASCL1, NEUROD1, and POU2F3 (SCLC-A, -N, and -P, respectively). To define the heterogeneity of tumors and their associated microenvironments across subtypes, we sequenced 155,098 transcriptomes from 21 human biospecimens, including 54,523 SCLC transcriptomes. We observe greater tumor diversity in SCLC than lung adenocarcinoma, driven by canonical, intermediate, and admixed subtypes. We discover a PLCG2-high SCLC phenotype with stem-like, pro-metastatic features that recurs across subtypes and predicts worse overall survival. SCLC exhibits greater immune sequestration and less immune infiltration than lung adenocarcinoma, and SCLC-N shows less immune infiltrate and greater T-cell dysfunction than SCLC-A. We identify a profibrotic, immunosuppressive monocyte/macrophage population in SCLC tumors that is particularly associated with the recurrent, PLCG2-high subpopulation. Chan et al. use single-cell transcriptome sequencing and imaging techniques to study the heterogeneity and tumor microenvironment of clinical small cell lung cancer specimens. This analysis identifies a PLCG2-high expressing subpopulation linked to metastasis and poor prognosis, and an enrichment of a monocyte/macrophage population with a profibrotic, immunosuppressive phenotype.
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影响因子：
8.8
作者：
Borromeo MD;Savage TK;Kollipara RK;He M;Augustyn A;Osborne JK;Girard L;Minna JD;Gazdar AF;Cobb MH;Johnson JE
通讯作者：
Johnson JE
影响因子：
20.4
作者：
Best, Sarah A.;Hess, Jonas B.;Sutherland, Kate D.
通讯作者：
Sutherland, Kate D.
影响因子：
6.2
作者：
Byers LA;Rudin CM
通讯作者：
Rudin CM
影响因子：
14.8
作者：
Efremova, Mirjana;Vento-Tormo, Miquel;Vento-Tormo, Roser
通讯作者：
Vento-Tormo, Roser
影响因子：
64.5
作者：
Azizi E;Carr AJ;Plitas G;Cornish AE;Konopacki C;Prabhakaran S;Nainys J;Wu K;Kiseliovas V;Setty M;Choi K;Fromme RM;Dao P;McKenney PT;Wasti RC;Kadaveru K;Mazutis L;Rudensky AY;Pe'er D
通讯作者：
Pe'er D