Publication

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

Authors: 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
Journal: Cancer Cell  Pubmed: 34653364   DOI: 10.1016/j.ccell.2021.09.008
Atlas: Memorial Sloan Kettering Cancer Center

Abstract

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.


Data Availability
FilesCRDC-GC/SB-CGC (dbGaP )Synapse (Open Access )
scRNA-seq Level 13560
scRNA-seq Level 2520
scRNA-seq Level 30208
scRNA-seq Level 40270
Level
Columns (11/25)
Filename
Atlas Name
Publications
Biospecimen
Assay
Level
Organ
Diagnosis
Data Access
Metadata
View
1163_Ru117...fastq.gz
HTAN MSK
HTA8_1009_1
scRNA-seq
Level 1
Lung NOS
Adenocarcinoma NOS
dbGaP
1163_Ru117...fastq.gz
HTAN MSK
HTA8_1009_1
scRNA-seq
Level 1
Lung NOS
Adenocarcinoma NOS
dbGaP
1188_Ru117...fastq.gz
HTAN MSK
HTA8_1009_2
scRNA-seq
Level 1
Lung NOS
Adenocarcinoma NOS
dbGaP
1163_Ru117...fastq.gz
HTAN MSK
HTA8_1009_1
scRNA-seq
Level 1
Lung NOS
Adenocarcinoma NOS
dbGaP
1188_Ru117...fastq.gz
HTAN MSK
HTA8_1009_2
scRNA-seq
Level 1
Lung NOS
Adenocarcinoma NOS
dbGaP
1163_Ru117...fastq.gz
HTAN MSK
HTA8_1009_1
scRNA-seq
Level 1
Lung NOS
Adenocarcinoma NOS
dbGaP
1188_Ru117...fastq.gz
HTAN MSK
HTA8_1009_2
scRNA-seq
Level 1
Lung NOS
Adenocarcinoma NOS
dbGaP
1189_Ru117...fastq.gz
HTAN MSK
HTA8_1009_3
scRNA-seq
Level 1
Lung NOS
Adenocarcinoma NOS
dbGaP
1189_Ru117...fastq.gz
HTAN MSK
HTA8_1009_3
scRNA-seq
Level 1
Lung NOS
Adenocarcinoma NOS
dbGaP
1188_Ru117...fastq.gz
HTAN MSK
HTA8_1009_2
scRNA-seq
Level 1
Lung NOS
Adenocarcinoma NOS
dbGaP
1189_Ru117...fastq.gz
HTAN MSK
HTA8_1009_3
scRNA-seq
Level 1
Lung NOS
Adenocarcinoma NOS
dbGaP
1559_1262C...fastq.gz
HTAN MSK
HTA8_1010_1
scRNA-seq
Level 1
Lung NOS
Adenocarcinoma NOS
dbGaP
1559_1262C...fastq.gz
HTAN MSK
HTA8_1010_1
scRNA-seq
Level 1
Lung NOS
Adenocarcinoma NOS
dbGaP
1189_Ru117...fastq.gz
HTAN MSK
HTA8_1009_3
scRNA-seq
Level 1
Lung NOS
Adenocarcinoma NOS
dbGaP
HTAN MSK
HTA8_1009_1
scRNA-seq
Level 3
Lung NOS
Adenocarcinoma NOS
Synapse
HTAN MSK
HTA8_1009_1
scRNA-seq
Level 3
Lung NOS
Adenocarcinoma NOS
Synapse
HTAN MSK
HTA8_1009_1
scRNA-seq
Level 3
Lung NOS
Adenocarcinoma NOS
Synapse
HTAN MSK
HTA8_1009_1
scRNA-seq
Level 3
Lung NOS
Adenocarcinoma NOS
Synapse
HTAN MSK
HTA8_1009_2
scRNA-seq
Level 3
Lung NOS
Adenocarcinoma NOS
Synapse
HTAN MSK
HTA8_1009_2
scRNA-seq
Level 3
Lung NOS
Adenocarcinoma NOS
Synapse
HTAN MSK
HTA8_1009_2
scRNA-seq
Level 3
Lung NOS
Adenocarcinoma NOS
Synapse
HTAN MSK
HTA8_1009_2
scRNA-seq
Level 3
Lung NOS
Adenocarcinoma NOS
Synapse
HTAN MSK
HTA8_1009_3
scRNA-seq
Level 3
Lung NOS
Adenocarcinoma NOS
Synapse
HTAN MSK
HTA8_1009_3
scRNA-seq
Level 3
Lung NOS
Adenocarcinoma NOS
Synapse
HTAN MSK
HTA8_1009_3
scRNA-seq
Level 3
Lung NOS
Adenocarcinoma NOS
Synapse
HTAN MSK
HTA8_1009_3
scRNA-seq
Level 3
Lung NOS
Adenocarcinoma NOS
Synapse
HTAN MSK
HTA8_1010_1
scRNA-seq
Level 3
Lung NOS
Adenocarcinoma NOS
Synapse
HTAN MSK
HTA8_1010_1
scRNA-seq
Level 3
Lung NOS
Adenocarcinoma NOS
Synapse
HTAN MSK
HTA8_1010_1
scRNA-seq
Level 3
Lung NOS
Adenocarcinoma NOS
Synapse
1663_Ru127...fastq.gz
HTAN MSK
HTA8_1011_1
scRNA-seq
Level 1
Lung NOS
Adenocarcinoma NOS
dbGaP
HTAN MSK
HTA8_1011_1
scRNA-seq
Level 3
Lung NOS
Adenocarcinoma NOS
Synapse
HTAN MSK
HTA8_1010_1
scRNA-seq
Level 3
Lung NOS
Adenocarcinoma NOS
Synapse
HTAN MSK
HTA8_1011_1
scRNA-seq
Level 3
Lung NOS
Adenocarcinoma NOS
Synapse
HTAN MSK
HTA8_1011_1
scRNA-seq
Level 3
Lung NOS
Adenocarcinoma NOS
Synapse
HTAN MSK
HTA8_1011_1
scRNA-seq
Level 3
Lung NOS
Adenocarcinoma NOS
Synapse
1559_1262C...fastq.gz
HTAN MSK
HTA8_1010_1
scRNA-seq
Level 1
Lung NOS
Adenocarcinoma NOS
dbGaP
1663_Ru127...fastq.gz
HTAN MSK
HTA8_1011_1
scRNA-seq
Level 1
Lung NOS
Adenocarcinoma NOS
dbGaP
HTAN MSK
HTA8_1021_1
scRNA-seq
Level 3
Lung NOS
Adenocarcinoma NOS
Synapse
HTAN MSK
HTA8_1021_1
scRNA-seq
Level 3
Lung NOS
Adenocarcinoma NOS
Synapse
HTAN MSK
HTA8_1021_1
scRNA-seq
Level 3
Lung NOS
Adenocarcinoma NOS
Synapse
HTAN MSK
HTA8_1021_1
scRNA-seq
Level 3
Lung NOS
Adenocarcinoma NOS
Synapse
HTAN MSK
HTA8_1022_1
scRNA-seq
Level 3
Lung NOS
Adenocarcinoma NOS
Synapse
HTAN MSK
HTA8_1022_1
scRNA-seq
Level 3
Lung NOS
Adenocarcinoma NOS
Synapse
HTAN MSK
HTA8_1022_1
scRNA-seq
Level 3
Lung NOS
Adenocarcinoma NOS
Synapse
HTAN MSK
HTA8_1022_1
scRNA-seq
Level 3
Lung NOS
Adenocarcinoma NOS
Synapse
HTAN MSK
HTA8_2001_1
scRNA-seq
Level 3
Lung NOS
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Synapse
HTAN MSK
HTA8_2001_1
scRNA-seq
Level 3
Lung NOS
Adenocarcinoma combined with other types of carcinoma
Synapse
HTAN MSK
HTA8_2001_1
scRNA-seq
Level 3
Lung NOS
Adenocarcinoma combined with other types of carcinoma
Synapse
HTAN MSK
HTA8_2001_1
scRNA-seq
Level 3
Lung NOS
Adenocarcinoma combined with other types of carcinoma
Synapse
HTAN MSK
HTA8_2002_1
scRNA-seq
Level 3
Lung NOS
Small cell neuroendocrine carcinoma
Synapse