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

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

Authors:	Chan, J. M.; Quintanal-Villalonga, Á; Gao, V. R.; Xie, Y.; Allaj, V.; Chaudhary, O.; Masilionis, I.; Egger, J.; Chow, A.; Walle, T.; Mattar, M.; Yarlagadda, D. V. K.; Wang, J. L.; Uddin, F.; Offin, M.; Ciampricotti, M.; Qeriqi, B.; Bahr, A.; de Stanchina, E.; Bhanot, U. K.; Lai, W. V.; Bott, M. J.; Jones, D. R.; Ruiz, A.; Baine, M. K.; Li, Y.; Rekhtman, N.; Poirier, J. T.; Nawy, T.; Sen, T.; Mazutis, L.; Hollmann, T. J.; Pe'er, D.; Rudin, C. M.
Article Title:	Signatures of plasticity, metastasis, and immunosuppression in an atlas of human small cell lung cancer
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. © 2021 Elsevier Inc.
Keywords:	metastasis; sclc; myeloid; single cell; scrna-seq; plcg2; tumor atlas
Journal Title:	Cancer Cell
Volume:	39
Issue:	11
ISSN:	1535-6108
Publisher:	Cell Press
Date Published:	2021-11-08
Start Page:	1479
End Page:	1496.e18
Language:	English
DOI:	10.1016/j.ccell.2021.09.008
PROVIDER:	scopus
PMCID:	PMC8628860
PUBMED:	34653364
DOI/URL:	https://www.scopus.com/inward/record.uri?eid=2-s2.0-85118495408&doi=10.1016%2fj.ccell.2021.09.008&partnerID=40&md5=ec39b9fd9f6b504374266f951e0b7876
Notes:	Article -- Export Date: 1 December 2021 -- Source: Scopus