Signatures of plasticity, metastasis, and immunosuppression in an atlas of human small cell lung cancer
Joseph M. Chan, Álvaro Quintanal-Villalonga, Vianne Ran Gao, Yubin Xie, Viola Allaj, Ojasvi Chaudhary, Ignas Masilionis, Jacklynn Egger, Andrew Chow, Thomas Walle, Marissa Mattar, Dig V.K. Yarlagadda, James L. Wang, Fathema Uddin, Michael Offin, Metamia Ciampricotti, Besnik Qeriqi, Amber Bahr, Elisa de Stanchina, Umesh K. Bhanot, W. Victoria Lai, Matthew J. Bott, David R. Jones, Arvin Ruiz, Marina K. Baine, Yanyun Li, Natasha Rekhtman, John T. Poirier, Tal Nawy, Triparna Sen, Linas Mazutis, Travis J. Hollmann, Dana Pe'er, Charles M. Rudin
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.
Datasets
1. Combined samples
Metadata
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treatment
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histo
cell_type_coarse
cell_type_fine
cell_type_general
clusters
cell_type_med
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assay_ontology_term_id
tissue_ontology_term_id
disease_ontology_term_id
organism_ontology_term_id
cell_type_ontology_term_id
suspension_type
HTAN_Biospecimen_ID
HTAN_Participant_ID
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cell_type
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RU1108a_Bambanker_Frozen4231 cells RU1134_Sort-Freeze3264 cells RU1108a_Bambanker2926 cells PleuralEffusion2549 cells RU1038_Sort-Freeze2025 cells RU1170g_Sort-Freeze1879 cells RU1170g_Freeze-Sort1419 cells PleuralEffusion2549 cells Platinum Doublet30101 cells Platinum Doublet,Immunotherapy24380 cells Platinum Doublet,PARP inhibitor,TMZ11294 cells Platinum Doublet,TKI4382 cells Platinum Doublet,Immunotherapy,TKI3209 cells Platinum Doublet,Immunotherapy,TMZ,Other chemotherapy,VEGF inhibitor2549 cells Platinum Doublet,Immunotherapy,TMZ,Other chemotherapy2488 cells Epithelial Stroma6108 cells HsapDv:000016819763 cells HsapDv:000014111294 cells HsapDv:000020610998 cells HsapDv:000016210800 cells HsapDv:000014910283 cells HANCESTRO:0005134630 cells UBERON:000204890384 cells UBERON:000002918594 cells NCBITaxon:9606147137 cells epithelial cell64302 cells endothelial cell3078 cells 10x 3' transcription profiling3857 cells small cell lung carcinoma77143 cells lung adenocarcinoma57679 cells pleural effusion6969 cells African American3209 cells 74-year-old human stage19763 cells 47-year-old human stage11294 cells 80-year-old human stage10998 cells 68-year-old human stage10800 cells 55-year-old human stage10283 cells 64-year-old human stage9933 cells 65-year-old human stage8718 cells 70-year-old human stage8060 cells 79-year-old human stage7760 cells 67-year-old human stage5255 cells 62-year-old human stage4873 cells 75-year-old human stage4420 cells 76-year-old human stage4361 cells 69-year-old human stage4148 cells 72-year-old human stage3811 cells 85-year-old human stage3174 cells 82-year-old human stage3053 cells 44-year-old human stage2909 cells 81-year-old human stage2488 cells 71-year-old human stage2050 cells 84-year-old human stage2025 cells 73-year-old human stage1300 cells 78-year-old human stage822 cells 77-year-old human stage666 cells 57-year-old human stage316 cells Analyze this study
Source data
https://cellxgene.cziscience.com/collections/62e8f058-9c37-48bc-9200-e767f318a8ec
Alias names
phs002371, HTAN MSK, PMID34653364, PMC8628860
Cite this study
Chan, J.M., Quintanal-Villalonga, A., Gao, V.R., Xie, Y., Allaj, V., Chaudhary, O., Masilionis, I., Egger, J., Chow, A., Walle, T. and Mattar, M., 2021. Signatures of plasticity, metastasis, and immunosuppression in an atlas of human small cell lung cancer. Cancer cell, 39(11), pp.1479-1496. https://doi.org/10.1016/j.ccell.2021.09.008
