| Literature DB >> 34653364 |
Joseph M Chan1, Álvaro Quintanal-Villalonga2, Vianne Ran Gao3, Yubin Xie3, Viola Allaj2, Ojasvi Chaudhary4, Ignas Masilionis4, Jacklynn Egger2, Andrew Chow2, Thomas Walle5, Marissa Mattar6, Dig V K Yarlagadda4, James L Wang7, Fathema Uddin2, Michael Offin2, Metamia Ciampricotti2, Besnik Qeriqi6, Amber Bahr6, Elisa de Stanchina8, Umesh K Bhanot9, W Victoria Lai2, Matthew J Bott10, David R Jones10, Arvin Ruiz11, Marina K Baine11, Yanyun Li11, Natasha Rekhtman11, John T Poirier12, Tal Nawy4, Triparna Sen13, Linas Mazutis14, Travis J Hollmann11, Dana Pe'er15, Charles M Rudin16.
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.Entities:
Keywords: PLCG2; SCLC; metastasis; myeloid; scRNA-seq; single cell; tumor atlas
Mesh：
Substances：
Year: 2021 PMID： 34653364 PMCID： PMC8628860 DOI： 10.1016/j.ccell.2021.09.008
Source DB: PubMed Journal: Cancer Cell ISSN： 1535-6108 Impact factor: 31.743