RT Journal Article
SR Electronic
T1 Single cell profiling reveals novel tumor and myeloid subpopulations in small cell lung cancer
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2020.12.01.406363
DO 10.1101/2020.12.01.406363
A1 Joseph M Chan
A1 Álvaro Quintanal-Villalonga
A1 Vianne Gao
A1 Yubin Xie
A1 Viola Allaj
A1 Ojasvi Chaudhary
A1 Ignas Masilionis
A1 Jacklynn Egger
A1 Andrew Chow
A1 Thomas Walle
A1 Marissa Mattar
A1 Dig VK Yarlagadda
A1 James L. Wang
A1 Fathema Uddin
A1 Michael Offin
A1 Metamia Ciampricotti
A1 Umesh K Bhanot
A1 W Victoria Lai
A1 Matthew J Bott
A1 David R Jones
A1 Arvin Ruiz
A1 Travis Hollmann
A1 John T Poirier
A1 Tal Nawy
A1 Linas Mazutis
A1 Triparna Sen
A1 Dana Pe’er
A1 Charles M Rudin
YR 2020
UL http://biorxiv.org/content/early/2020/12/02/2020.12.01.406363.abstract
AB 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), which are associated with distinct therapeutic vulnerabilities. To define the heterogeneity of tumors and their associated microenvironments across subtypes, we sequenced 54,523 cellular transcriptomes from 21 human biospecimens. Our single-cell SCLC atlas reveals tumor diversity exceeding lung adenocarcinoma, driven by canonical, intermediate, and admixed subtypes. We discovered a PLCG2-high tumor cell population with stem-like, pro-metastatic features that recurs across subtypes and predicts worse overall survival, and manipulation of PLCG2 expression in cells confirms correlation with key metastatic markers. Treatment and subtype are associated with substantial phenotypic changes in the SCLC immune microenvironment, with greater T-cell dysfunction in SCLC-N than SCLC-A. Moreover, the recurrent, PLCG2-high subclone is associated with exhausted CD8+ T-cells and a pro-fibrotic, immunosuppressive monocyte/macrophage population, suggesting possible tumor-immune coordination to promote metastasis.Competing Interest StatementCMR has consulted regarding oncology drug development with AbbVie, Amgen, Ascentage, Astra Zeneca, Bicycle, Celgene, Daiichi Sankyo, Genentech/Roche, Ipsen, Jazz, Lilly, Pfizer, PharmaMar, Syros, and Vavotek. He serves on the scientific advisory boards of Bridge Medicines, Earli, and Harpoon Therapeutics.