Systematic analysis of the transcriptome in small-cell carcinoma of the oesophagus reveals its immune microenvironment.
Systematic analysis of the transcriptome in small-cell carcinoma of the oesophagus reveals its immune microenvironment.
复制标题
对食管小细胞癌转录组的系统分析揭示了其免疫微环境。
DOI：
10.1002/cti2.1173
复制
发表时间：
2020
影响因子：
5.8
通讯作者：
Wang F
中科院分区：
文献类型：
--
作者：
Zhao Q;Chen YX;Wu QN;Zhang C;Liu M;Wang YN;Feng YF;Hu JJ;Fu JH;Yang H;Qi JJ;Wang ZX;Lu YX;Sheng H;Liu ZX;Zuo ZX;Zheng J;Yun JP;Bei JX;Jia WH;Lin DX;Xu RH;Wang F
Although the genomic landscape of small‐cell carcinoma of the oesophagus (SCCE) has been dissected, its transcriptome‐level aberration and immune microenvironment status are unknown. Using ultra‐deep whole transcriptome sequencing, we analysed the expression profile of nine paired SCCE samples and compared the transcriptome with public transcriptomic data set of normal oesophageal mucosa and other cancer types. Based on the transcriptome data, the immune signatures were investigated. The genomic data of 55 SCCE samples were also applied for immune checkpoint blockade therapy (ICBT) biomarker evaluation including microsatellite instability (MSI) status, tumor mutation burden (TMB) and neoantigen burden (TNB). Also, we evaluated the CD8, CD68 and programmed death‐ligand 1 (PD‐L1) in 62 retrospective SCCE samples with IHC assay. Differential expression analysis revealed that the cell cycle, p53, and Wnt pathways are significantly deregulated in SCCE. Immune microenvironment analysis showed that high leucocyte infiltration and adaptive immune resistance did occur in certain individuals, while the majority showed a relatively suppressive immune status. Immune checkpoints such as CD276 and LAG‐3 were upregulated, and higher M2 macrophage infiltration in tumor tissues. Furthermore, normal tissues adjacent to the tumors of SCCE presented a more activated inflammatory status than tumor‐free healthy controls. These observations showed that ICBT might benefit SCCE patients. As the critical biomarker of ICBT, TMB of SCCE was 3.64 with the predictive objective response rate 13.2%, while the PD‐L1‐positive rate was 43%. Our study systematically characterized the immune microenvironment in small‐cell carcinoma of the esophagus and provided evidence that several patients with SCCE may benefit from immune checkpoint blockade therapy. In this study, transcriptomic aberrance and immune microenvironment of small‐cell carcinoma of the esophagus (SCCE) was comprehensively characterized with transcriptome and immunohistochemistry analysis. Assessment of immune checkpoint blockade (ICB) treatment biomarkers provides a rationale for use of ICB treatment in patients with SCCE.
登录
查看更多内容
DOI：
10.4049/jimmunol.1700893
发表时间：
2017-11-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Jurtz V;Paul S;Andreatta M;Marcatili P;Peters B;Nielsen M
通讯作者：
Nielsen M
影响因子：
16.6
作者：
Aran D;Camarda R;Odegaard J;Paik H;Oskotsky B;Krings G;Goga A;Sirota M;Butte AJ
通讯作者：
Butte AJ
影响因子：
4.6
作者：
Bonneville R;Krook MA;Kautto EA;Miya J;Wing MR;Chen HZ;Reeser JW;Yu L;Roychowdhury S
通讯作者：
Roychowdhury S
影响因子：
--
作者：
Kang, Jingjing;Luo, Yang;Hui, Zhouguang
通讯作者：
Hui, Zhouguang
影响因子：
3.1
作者：
Kasten BB;Arend RC;Katre AA;Kim H;Fan J;Ferrone S;Zinn KR;Buchsbaum DJ
通讯作者：
Buchsbaum DJ