Signatures of plasticity, metastasis, and immunosuppression in an atlas of human small cell lung cancer

被引：254

作者：

Chan, Joseph M. ^{[1
,2
]}

Quintanal-Villalonga, Alvaro ^{[1
]}

Gao, Vianne Ran ^{[2
,13
]}

Xie, Yubin ^{[2
,13
]}

Allaj, Viola ^{[1
]}

Chaudhary, Ojasvi ^{[2
]}

Masilionis, Ignas ^{[2
]}

Egger, Jacklynn ^{[1
]}

Chow, Andrew ^{[1
]}

Walle, Thomas ^{[3
]}

Mattar, Marissa ^{[4
]}

Yarlagadda, Dig V. K. ^{[2
]}

Wang, James L. ^{[5
]}

Uddin, Fathema ^{[1
]}

Offin, Michael ^{[1
]}

Ciampricotti, Metamia ^{[1
]}

Qeriqi, Besnik ^{[4
]}

Bahr, Amber ^{[4
]}

de Stanchina, Elisa ^{[4
,6
]}

Bhanot, Umesh K. ^{[7
]}

Lai, W. Victoria ^{[1
]}

Bott, Matthew J. ^{[8
]}

Jones, David R. ^{[8
]}

Ruiz, Arvin ^{[9
]}

Baine, Marina K. ^{[9
]}

Li, Yanyun ^{[9
]}

Rekhtman, Natasha ^{[9
]}

Poirier, John T. ^{[10
]}

Nawy, Tal ^{[2
]}

Sen, Triparna ^{[1
,13
]}

Mazutis, Linas ^{[11
]}

Hollmann, Travis J. ^{[9
]}

Pe'er, Dana ^{[2
,12
]}

Rudin, Charles M. ^{[1
,6
,13
]}

机构：

[1] Mem Sloan Kettering Canc Ctr, Dept Med, Thorac Oncol Serv, New York, NY 10065 USA

[2] Mem Sloan Kettering Canc Ctr, Sloan Kettering Inst, Program Computat & Syst Biol, New York, NY 10016 USA

[3] German Canc Res Ctr, Clin Cooperat Unit Virotherapy, German Canc Consortium DKTK, Dept Med Oncol,Natl Ctr Tumor Dis NCT, Heidelberg, Germany

[4] Mem Sloan Kettering Canc Ctr, Antitumor Assessment Core Facil, New York, NY 10065 USA

[5] Columbia Univ, Dept Comp Sci, New York, NY 10027 USA

[6] Mem Sloan Kettering Canc Ctr, Mol Pharmacol Program, New York, NY 10065 USA

[7] Mem Sloan Kettering Canc Ctr, Precis Pathol Ctr, New York, NY 10065 USA

[8] Mem Sloan Kettering Canc Ctr, Fiona & Stanley Druckenmiller Ctr Lung Canc Res, Dept Surg, Thorac Serv, New York, NY 10065 USA

[9] Mem Sloan Kettering Canc Ctr, Dept Pathol, New York, NY 10065 USA

[10] New York Univ Langone Hlth, Perlmutter Canc Ctr, New York, NY 10065 USA

[11] Vilnius Univ, Inst Biotechnol, Vilnius, Lithuania

[12] Mem Sloan Kettering Canc Ctr, Parker Inst Canc Immunotherapy, New York, NY 10065 USA

[13] Weill Cornell Med Coll, New York, NY 10065 USA

来源：

CANCER CELL | 2021年 / 39卷 / 11期

关键词：

ABERRANT EXPRESSION; SUBTYPES; YAP1; INHIBITION; NEUROD1; DEFINES; TUMORS; GROWTH; ASCL1; GENE;

D O I：

10.1016/j.ccell.2021.09.008

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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.

引用

页码：1479 / +

页数：37

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