Cell-autonomous immune gene expression is repressed in pulmonary neuroendocrine cells and small cell lung cancer

被引：62

作者：

Cai, Ling ^{[1
,2
,3
]}

Liu, Hongyu ^{[1
,4
]}

Huang, Fang ^{[2
]}

Fujimoto, Junya ^{[5
]}

Girard, Luc ^{[3
,6
,7
]}

Chen, Jun ^{[4
,8
]}

Li, Yongwen ^{[4
]}

Zhang, Yu-An ^{[6
]}

Deb, Dhruba ^{[6
]}

Stastny, Victor ^{[6
]}

Pozo, Karine ^{[9
]}

Kuo, Christin S. ^{[10
]}

Jia, Gaoxiang ^{[1
]}

Yang, Chendong ^{[2
]}

Zou, Wei ^{[11
]}

Alomar, Adeeb ^{[6
]}

Huffman, Kenneth ^{[6
]}

Papari-Zareei, Mahboubeh ^{[6
]}

Yang, Lin ^{[12
]}

Drapkin, Benjamin ^{[3
,6
,9
]}

Akbay, Esra A. ^{[13
]}

Shames, David S. ^{[11
]}

Wistuba, Ignacio I. ^{[5
]}

Wang, Tao ^{[1
,3
]}

Johnson, Jane E. ^{[3
,7
,14
]}

Xiao, Guanghua ^{[1
,3
,15
]}

DeBerardinis, Ralph J. ^{[2
,3
,16
]}

Minna, John D. ^{[3
,6
,7
,9
]}

Xie, Yang ^{[1
,3
,15
]}

Gazdar, Adi F. ^{[3
,6
,13
]}

机构：

[1] UT Southwestern Med Ctr, Dept Populat & Data Sci, Quantitat Biomed Res Ctr, Dallas, TX 75390 USA

[2] UT Southwestern Med Ctr, Childrens Res Inst, Dallas, TX 75390 USA

[3] UT Southwestern Med Ctr, Simmons Comprehens Canc Ctr, Dallas, TX 75390 USA

[4] Tianjin Med Univ, Tianjin Lung Canc Inst, Gen Hosp, Tianjin Key Lab Lung Canc Metastasis & Tumor Micr, Tianjin, Peoples R China

[5] Univ Texas MD Anderson Canc Ctr, Dept Translat Mol Pathol, Houston, TX 77030 USA

[6] UT Southwestern Med Ctr, Hamon Ctr Therapeut Oncol Res, Dallas, TX 75390 USA

[7] UT Southwestern Med Ctr, Dept Pharmacol, Dallas, TX 75390 USA

[8] Tianjin Med Univ, Gen Hosp, Tianjin Lung Canc Inst, Dept Lung Canc Surg, Tianjin, Peoples R China

[9] UT Southwestern Med Ctr, Dept Internal Med, Dallas, TX 75390 USA

[10] Stanford Univ, Dept Pediat, Stanford, CA 94305 USA

[11] Genentech Inc, Dept Oncol Biomarker Dev, San Francisco, CA 94080 USA

[12] Chinese Acad Med Sci & Peking Union Med Coll, Canc Hosp, Natl Ctr, Dept Pathol, Beijing, Peoples R China

[13] UT Southwestern Med Ctr, Dept Pathol, Dallas, TX USA

[14] UT Southwestern Med Ctr, Dept Neurosci, Dallas, TX USA

[15] UT Southwestern Med Ctr, Dept Bioinformat, Dallas, TX 75390 USA

[16] UT Southwestern Med Ctr, Howard Hughes Med Inst, Dallas, TX USA

来源：

COMMUNICATIONS BIOLOGY | 2021年 / 4卷 / 01期

基金：

美国国家卫生研究院;

关键词：

SET ENRICHMENT ANALYSIS; INFLUENZA-VIRUS; INNATE IMMUNITY; MESSENGER-RNA; HETEROGENEITY; SIGNATURES; LANDSCAPE; PROTEIN; GENOME; MOUSE;

D O I：

10.1038/s42003-021-01842-7

中图分类号：

Q [生物科学];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

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