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Signatures of plasticity, metastasis, and immunosuppression in an atlas of human small cell lung cancer
- Source :
- Cancer Cell, Cancer cell, Cambridge, MA : Cell Press, 2021, vol. 39, no. 11, p. 1479-1515
- Publication Year :
- 2021
-
Abstract
- Summary 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.
- Subjects :
- Cancer Research
Myeloid
Lung Neoplasms
medicine.medical_treatment
Cell Plasticity
Biology
Malignancy
Article
Metastasis
Immune system
medicine
Humans
Neoplasm Metastasis
neoplasms
Lung
Phospholipase C gamma
Sequence Analysis, RNA
Gene Expression Profiling
Immunosuppression
medicine.disease
Prognosis
Phenotype
Small Cell Lung Carcinoma
Survival Analysis
humanities
respiratory tract diseases
metastasis
myeloid
PLCG2
SCLC
scRNA-seq
single cell
tumor atlas
medicine.anatomical_structure
Oncology
Cancer research
Adenocarcinoma
Single-Cell Analysis
Subjects
Details
- Language :
- English
- ISSN :
- 15356108 and 18783686
- Database :
- OpenAIRE
- Journal :
- Cancer Cell, Cancer cell, Cambridge, MA : Cell Press, 2021, vol. 39, no. 11, p. 1479-1515
- Accession number :
- edsair.doi.dedup.....062d8b8d1c3b66795a51a7b9674b79e2