干旱区生态环境知识资源中心(Arid): ASCL1 promotes tumor progression through cell-autonomous signaling and immune modulation in a subset of lung adenocarcinoma

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DOI	10.1016/j.canlet.2020.06.002
	ASCL1 promotes tumor progression through cell-autonomous signaling and immune modulation in a subset of lung adenocarcinoma
	Miyashita, Naoya; Horie, Masafumi; Mikami, Yu; Urushiyama, Hirokazu; Fukuda, Kensuke; Miyakawa, Kazuko; Matsuzaki, Hirotaka; Makita, Kosuke; Morishita, Yasuyuki; Harada, Hiroaki; Backman, Max; Lindskog, Cecilia; Brunnstrom, Hans; Micke, Patrick; Nagase, Takahide; Saito, Akira
通讯作者	Saito, A
来源期刊	CANCER LETTERS
ISSN	0304-3835
EISSN	1872-7980
出版年	2020
卷号	489 页码:121-132
英文摘要	The master regulator of neuroendocrine differentiation, achaete-scute complex homolog 1 (ASCL1) defines a subgroup of lung adenocarcinoma. However, the mechanistic role of ASCL1 in lung tumorigenesis and its relation to the immune microenvironment is principally unknown. Here, the immune landscape of ASCL1-positive lung adenocarcinomas was characterized by immunohistochemistry. Furthermore, ASCL1 was transduced in mouse lung adenocarcinoma cell lines and comparative RNA-sequencing and secretome analyses were performed. The effects of ASCL1 on tumorigenesis were explored in an orthotopic syngeneic transplantation model. ASCL1-positive lung adenocarcinomas revealed lower infiltration of CD8(+), CD4(+), CD20(+), and FOXP3(+) lymphocytes and CD163(+) macrophages indicating an immune desert phenotype. Ectopic ASCL1 upregulated cyclin transcript levels, stimulated cell proliferation, and enhanced tumor growth in mice. ASCL1 suppressed secretion of chemokines, including CCL20, CXCL2, CXCL10, and CXCL16, indicating effects on immune cell trafficking. In accordance with lower lymphocytes infiltration, ASCL1-positive lung adenocarcinomas demonstrated lower abundance of CXCR3-and CCR6-expressing cells. In conclusion, ASCL1 mediates its tumor-promoting effect not only through cell-autonomous signaling but also by modulating chemokine production and immune responses. These findings suggest that ASCL1-positive tumors represent a clinically relevant lung cancer entity.
英文关键词	Lungadenocarcinoma ASCL1 Chemokine Neuroendocrine Immunotherapy
类型	Article
语种	英语
收录类别	SCI-E
WOS记录号	WOS:000570246700013
WOS关键词	CANCER-IMMUNITY ; NEUROENDOCRINE ; CHEMOKINES
WOS类目	Oncology
WOS研究方向	Oncology
资源类型	期刊论文
条目标识符	http://119.78.100.177/qdio/handle/2XILL650/326350
作者单位	[Miyashita, Naoya; Horie, Masafumi; Mikami, Yu; Urushiyama, Hirokazu; Fukuda, Kensuke; Miyakawa, Kazuko; Matsuzaki, Hirotaka; Makita, Kosuke; Nagase, Takahide; Saito, Akira] Univ Tokyo, Grad Sch Med, Dept Resp Med, Bunkyo Ku, 7-3-1 Hongo, Tokyo 1130033, Japan; [Horie, Masafumi] Osaka Univ, Grad Sch Med, Dept Canc Genome Informat, 2-2 Yamadaoka, Suita, Osaka 5650871, Japan; [Mikami, Yu] Univ North Carolina Chapel Hill, Marsico Lung Inst, Cyst Fibrosis Res Ctr, Chapel Hill, NC USA; [Makita, Kosuke] McGill Univ, Meakins Christie Labs, Res Inst, Hlth Ctr, Montreal, PQ, Canada; [Morishita, Yasuyuki] Univ Tokyo, Grad Sch Med, Dept Mol Pathol, Bunkyo Ku, 7-3-1 Hongo, Tokyo 1130033, Japan; [Harada, Hiroaki] Univ Tokyo, Grad Sch Med, Dept Allergy & Rheumatol, Bunkyo Ku, 7-3-1 Hongo, Tokyo 1130033, Japan; [Backman, Max; Lindskog, Cecilia; Micke, Patrick] Uppsala Univ, Dept Immunol Genet & Pathol, SE-75185 Uppsala, Sweden; [Brunnstrom, Hans] Lund Univ, Dept Clin Sci Lund, Lab Med Reg Skane, Pathol, SE-22185 Lund, Sw...
推荐引用方式 GB/T 7714	Miyashita, Naoya,Horie, Masafumi,Mikami, Yu,et al. ASCL1 promotes tumor progression through cell-autonomous signaling and immune modulation in a subset of lung adenocarcinoma[J],2020,489:121-132.
APA	Miyashita, Naoya.,Horie, Masafumi.,Mikami, Yu.,Urushiyama, Hirokazu.,Fukuda, Kensuke.,...&Saito, Akira.(2020).ASCL1 promotes tumor progression through cell-autonomous signaling and immune modulation in a subset of lung adenocarcinoma.CANCER LETTERS,489,121-132.
MLA	Miyashita, Naoya,et al."ASCL1 promotes tumor progression through cell-autonomous signaling and immune modulation in a subset of lung adenocarcinoma".CANCER LETTERS 489(2020):121-132.