| Literature DB >> 33750914 |
Ling Cai1,2,3, Hongyu Liu4,5, Fang Huang6, Junya Fujimoto7, Luc Girard8,9,10, Jun Chen5,11, Yongwen Li5, Yu-An Zhang9, Dhruba Deb9, Victor Stastny9, Karine Pozo12, Christin S Kuo13, Gaoxiang Jia4, Chendong Yang6, Wei Zou14, Adeeb Alomar9, Kenneth Huffman9, Mahboubeh Papari-Zareei9, Lin Yang15, Benjamin Drapkin8,9,12, Esra A Akbay16, David S Shames14, Ignacio I Wistuba7, Tao Wang4,8, Jane E Johnson8,10,17, Guanghua Xiao4,8,18, Ralph J DeBerardinis6,8,19, John D Minna20,21,22,23, Yang Xie24,25,26, Adi F Gazdar8,9,16.
Abstract
Small cell lung cancer (SCLC) is classified as a high-grade neuroendocrine (NE) tumor, but a subset of SCLC has been termed "variant" due to the loss of NE characteristics. In this study, we computed NE scores for patient-derived SCLC cell lines and xenografts, as well as human tumors. We aligned NE properties with transcription factor-defined molecular subtypes. Then we investigated the different immune phenotypes associated with high and low NE scores. We found repression of immune response genes as a shared feature between classic SCLC and pulmonary neuroendocrine cells of the healthy lung. With loss of NE fate, variant SCLC tumors regain cell-autonomous immune gene expression and exhibit higher tumor-immune interactions. Pan-cancer analysis revealed this NE lineage-specific immune phenotype in other cancers. Additionally, we observed MHC I re-expression in SCLC upon development of chemoresistance. These findings may help guide the design of treatment regimens in SCLC.Entities:
Year: 2021 PMID： 33750914 PMCID： PMC7943563 DOI： 10.1038/s42003-021-01842-7
Source DB: PubMed Journal: Commun Biol ISSN： 2399-3642