干旱区生态环境知识资源中心(Arid): Transcription factor RUNX3 promotes CD8(+) T cell recruitment by CCL3 and CCL20 in lung adenocarcinoma immune microenvironment

Arid

DOI	10.1002/jcb.29587
	Transcription factor RUNX3 promotes CD8(+) T cell recruitment by CCL3 and CCL20 in lung adenocarcinoma immune microenvironment
	Song, Qian 1,2; Shang, Jun 3; Zhang, Chufan 1,2; Chen, Jianing 4; Zhang, Lanlin 1,2; Wu, Xianghua 1,2
通讯作者	Wu, Xianghua
来源期刊	JOURNAL OF CELLULAR BIOCHEMISTRY
ISSN	0730-2312
EISSN	1097-4644
出版年	2020
卷号	121 期号:5-6 页码:3208-3220
英文摘要	Considering the existence of immune-desert in tumor microenvironment, the clinical efficacy of immunotherapy for lung adenocarcinoma is limited. This study aims to investigate the ability of transcription factors in regulating tumor immune microenvironment in lung adenocarcinoma. RNA-seq data were collected from the The Cancer Genome Atlas database. The relationships between transcription factors and immune infiltrates were assessed. Runt-related transcription factor 3 (RUNX3)-associated immune pathways were investigated by the Kyoto Encyclopedia of Genes and Genomes, Gene Ontology, and Gene set enrichment analysis. Upregulated chemokines in the RUNX3-overexpressed cell line were determined by quantitative real-time polymerase chain reaction, western blot, and enzyme-linked immunosorbent assay. These chemokines were further confirmed in RUNX3-downregulated cell lines. Immunochemistry was conducted to determine the expression of RUNX3, CCL3, CCL20, and the numbers of CD8(+) T lymphocytes in human lung cancer tissues. Chemokine receptors in CD8(+) T cells were explored by flow cytometry and immunofluorescence. T cell recruitment was investigated by transwell assay. After screening 406 transcription factors, RUNX3 was found strongly correlated T cells, cytotoxic lymphocytes, and CD8(+) T cells. RUNX3 was associated with a variety of immunomodulators, including LAG3, CTLA-4, PD-1, and TIGIT. More importantly, RUNX3 was involved in immune-related pathways, especially immune cell migration-related pathways. Further investigation exhibited RUNX3 could upregulate CCL3 and CCL20 whose receptors CCR5 and CCR6 were upregulated in CD8(+) effector T cells, while downregulation of RUNX3 decreased the expression of CCL3 and CCL20 and the infiltration of CD8(+) T cells in RUNX3-downregulated lung cancer cell lines. Immunochemistry exhibited positive correlations of RUNX3 with CCL3 and CD8(+) T cells in clinical lung adenocarcinoma samples. The chemotaxis assay proved RUNX3 could promote CD8(+) T cell recruitment by upregulating CCL3 and CCL20. This study unearths RUNX3 related molecular mechanisms of tumor immune microenvironment and may reverse the immune-desert condition in lung adenocarcinoma and be combined with immune checkpoint blockade and adoptive cell therapy.
英文关键词	chemokine lung adenocarcinoma RUNX3 T cell recruitment
类型	Article
语种	英语
国家	Peoples R China
收录类别	SCI-E
WOS记录号	WOS:000505285400001
WOS关键词	FUNCTIONAL EXPRESSION ; CANCER ; EFFECTOR ; MEMORY ; DIFFERENTIATION ; GENE
WOS类目	Biochemistry & Molecular Biology ; Cell Biology
WOS研究方向	Biochemistry & Molecular Biology ; Cell Biology
EI主题词	2020-01-03
资源类型	期刊论文
条目标识符	http://119.78.100.177/qdio/handle/2XILL650/312380
作者单位	1.Fudan Univ, Shanghai Canc Ctr, Dept Med Oncol, 270 Dong An Rd, Shanghai 200032, Peoples R China; 2.Fudan Univ, Shanghai Med Coll, Dept Oncol, Shanghai, Peoples R China; 3.Fudan Univ, Sch Life Sci, Shanghai, Peoples R China; 4.Soochow Univ, Coll Med, Affiliated Hosp 1, Dept Hematol, Suzhou, Peoples R China
推荐引用方式 GB/T 7714	Song, Qian,Shang, Jun,Zhang, Chufan,et al. Transcription factor RUNX3 promotes CD8(+) T cell recruitment by CCL3 and CCL20 in lung adenocarcinoma immune microenvironment[J],2020,121(5-6):3208-3220.
APA	Song, Qian,Shang, Jun,Zhang, Chufan,Chen, Jianing,Zhang, Lanlin,&Wu, Xianghua.(2020).Transcription factor RUNX3 promotes CD8(+) T cell recruitment by CCL3 and CCL20 in lung adenocarcinoma immune microenvironment.JOURNAL OF CELLULAR BIOCHEMISTRY,121(5-6),3208-3220.
MLA	Song, Qian,et al."Transcription factor RUNX3 promotes CD8(+) T cell recruitment by CCL3 and CCL20 in lung adenocarcinoma immune microenvironment".JOURNAL OF CELLULAR BIOCHEMISTRY 121.5-6(2020):3208-3220.