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

被引：216

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

共 109 条

[71] FGFR1 Cooperates with EGFR in Lung Cancer Oncogenesis, and Their Combined Inhibition Shows Improved Efficacy
Quintanal-Villalonga, Alvaro
Molina-Pinelo, Sonia
Cirauqui, Cristina
Ojeda-Marquez, Laura
Marrugal, Angela
Suarez, Rocio
Conde, Esther
Ponce-Aix, Santiago
Enguita, Ana Belen
Carnero, Amancio
Ferrer, Irene
Paz-Ares, Luis
[J]. JOURNAL OF THORACIC ONCOLOGY, 2019, 14 (04) : 641 - 655
[72] limma powers differential expression analyses for RNA-sequencing and microarray studies
Ritchie, Matthew E.
Phipson, Belinda
Wu, Di
Hu, Yifang
Law, Charity W.
Shi, Wei
Smyth, Gordon K.
[J]. NUCLEIC ACIDS RESEARCH, 2015, 43 (07) : e47
[73] Small-cell lung cancer
Rudin, Charles M.
Brambilla, Elisabeth
Faivre-Finn, Corinne
Sage, Julien
[J]. NATURE REVIEWS DISEASE PRIMERS, 2021, 7 (01)
[74] Molecular subtypes of small cell lung cancer: a synthesis of human and mouse model data
Rudin, Charles M.
Poirier, John T.
Byers, Lauren Averett
Dive, Caroline
Dowlati, Afshin
George, Julie
Heymach, John, V
Johnson, Jane E.
Lehman, Jonathan M.
MacPherson, David
Massion, Pierre P.
Minna, John D.
Oliver, Trudy G.
Quaranta, Vito
Sage, Julien
Thomas, Roman K.
Vakoc, Christopher R.
Gazdar, Adi F.
[J]. NATURE REVIEWS CANCER, 2019, 19 (05) : 289 - 297
[75] Comprehensive genomic analysis identifies SOX2 as a frequently amplified gene in small-cell lung cancer
Rudin, Charles M.
Durinck, Steffen
Stawiski, Eric W.
Poirier, John T.
Modrusan, Zora
Shames, David S.
Bergbower, Emily A.
Guan, Yinghui
Shin, James
Guillory, Joseph
Rivers, Celina Sanchez
Foo, Catherine K.
Bhatt, Deepali
Stinson, Jeremy
Gnad, Florian
Haverty, Peter M.
Gentleman, Robert
Chaudhuri, Subhra
Janakiraman, Vasantharajan
Jaiswal, Bijay S.
Parikh, Chaitali
Yuan, Wenlin
Zhang, Zemin
Koeppen, Hartmut
Wu, Thomas D.
Stern, Howard M.
Yauch, Robert L.
Huffman, Kenneth E.
Paskulin, Diego D.
Illei, Peter B.
Varella-Garcia, Marileila
Gazdar, Adi F.
de Sauvage, Frederic J.
Bourgon, Richard
Minna, John D.
Brock, Malcolm V.
Seshagiri, Somasekar
[J]. NATURE GENETICS, 2012, 44 (10) : 1111 - +
[76] Unravelling the biology of SCLC: implications for therapy
Sabari, Joshua K.
Lok, Benjamin H.
Laird, James H.
Poirier, John T.
Rudin, Charles M.
[J]. NATURE REVIEWS CLINICAL ONCOLOGY, 2017, 14 (09) : 549 - 561
[77] A DLL3-targeted antibody-drug conjugate eradicates high-grade pulmonary neuroendocrine tumor-initiating cells in vivo
Saunders, Laura R.
Bankovich, Alexander J.
Anderson, Wade C.
Aujay, Monette A.
Bheddah, Sheila
Black, KristenAnn
Desai, Radhika
Escarpe, Paul A.
Hampl, Johannes
Laysang, Amy
Liu, David
Lopez-Molina, Javier
Milton, Milly
Park, Albert
Pysz, Marybeth A.
Shao, Hui
Slingerland, Brian
Torgov, Michael
Williams, Samuel A.
Foord, Orit
Howard, Philip
Jassem, Jacek
Badzio, Andrzej
Czapiewski, Piotr
Harpole, David H.
Dowlati, Afshin
Massion, Pierre P.
Travis, William D.
Pietanza, M. Catherine
Poirier, J. T.
Rudin, Charles M.
Stull, Robert A.
Dylla, Scott J.
[J]. SCIENCE TRANSLATIONAL MEDICINE, 2015, 7 (302)
[78] Zac1 Regulates Cell Cycle Arrest in Neuronal Progenitors via Tcf4
Schmidt-Edelkraut, Udo
Daniel, Guillaume
Hoffmann, Anke
Spengler, Dietmar
[J]. MOLECULAR AND CELLULAR BIOLOGY, 2014, 34 (06) : 1020 - 1030
[79] Seabold S, 2010, P 9 PYTH SCI C, P57, DOI DOI 10.25080/MAJORA-92BF1922-011
[80] Prognostic value of tumor-infiltrating FoxP3+ regulatory T cells in cancers: a systematic review and meta-analysis
Shang, Bin
Liu, Yao
Jiang, Shu-juan
Liu, Yi
[J]. SCIENTIFIC REPORTS, 2015, 5

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