干旱区生态环境知识资源中心(Arid): Neuroendocrine subtypes of small cell lung cancer differ in terms of immune microenvironment and checkpoint molecule distribution

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DOI	10.1002/1878-0261.12741
	Neuroendocrine subtypes of small cell lung cancer differ in terms of immune microenvironment and checkpoint molecule distribution
	Dora, David; Rivard, Christopher; Yu, Hui; Bunn, Paul; Suda, Kenichi; Ren, Shengxiang; Pickard, Shivaun Lueke; Laszlo, Viktoria; Harko, Tunde; Megyesfalvi, Zsolt; Moldvay, Judit; Hirsch, Fred R.; Dome, Balazs; Lohinai, Zoltan
通讯作者	Dome, B
来源期刊	MOLECULAR ONCOLOGY
ISSN	1574-7891
EISSN	1878-0261
出版年	2020
卷号	14 期号:9 页码:1947-1965
英文摘要	Small cell lung cancer (SCLC) has recently been subcategorized into neuroendocrine (NE)-high and NE-low subtypes showing 'immune desert' and 'immune oasis' phenotypes, respectively. Here, we aimed to characterize the tumor microenvironment according to immune checkpoints and NE subtypes in human SCLC tissue samples at the protein level. In this cross-sectional study, we included 32 primary tumors and matched lymph node (LN) metastases of resected early-stage, histologically confirmed SCLC patients, which were previously clustered into NE subtypes using NE-associated key RNA genes. Immunohistochemistry (IHC) was performed on formalin-fixed paraffin-embedded TMAs with antibodies against CD45, CD3, CD8, MHCII, TIM3, immune checkpoint poliovirus receptor (PVR), and indoleamine 2,3-dioxygenase (IDO). The stroma was significantly more infiltrated by immune cells both in primary tumors and in LN metastases compared to tumor nests. Immune cell (CD45(+)cell) density was significantly higher in tumor nests (P = 0.019), with increased CD8(+)effector T-cell infiltration (P = 0.003) in NE-low vs NE-high tumors. The expression of IDO was confirmed on stromal and endothelial cells and was positively correlated with higher immune cell density both in primary tumors and in LN metastases, regardless of the NE pattern. Expression of IDO and PVR in tumor nests was significantly higher in NE-low primary tumors (vs NE-high,P < 0.05). We also found significantly higher MHC II expression by malignant cells in NE-low (vs NE-high,P = 0.004) tumors. TIM3 expression was significantly increased in NE-low (vs NE-high,P < 0.05) tumors and in LN metastases (vs primary tumors,P < 0.05). To our knowledge, this is the first human study that demonstratesin situthat NE-low SCLCs are associated with increased immune cell infiltration compared to NE-high tumors. PVR, IDO, MHCII, and TIM3 are emerging checkpoints in SCLC, with increased expression in the NE-low subtype, providing key insight for further prospective studies on potential biomarkers and targets for SCLC immunotherapies.
英文关键词	neuroendocrine proteomics SCLC tumor microenvironment tumor-infiltrating immune cells
类型	Article
语种	英语
开放获取类型	DOAJ Gold, Green Published, Green Accepted
收录类别	SCI-E
WOS记录号	WOS:000549512800001
WOS关键词	TUMOR-INFILTRATING LYMPHOCYTES ; CD8(+) T-CELLS ; INDOLEAMINE 2,3-DIOXYGENASE ; EXPRESSION ; OVEREXPRESSION ; CD155 ; TIM-3 ; HETEROGENEITY ; MACROPHAGE ; PROGNOSIS
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/2XILL650/325078
作者单位	[Dora, David] Semmelweis Univ, Fac Med, Dept Anat Histol & Embryol, Budapest, Hungary; [Rivard, Christopher; Yu, Hui; Bunn, Paul; Pickard, Shivaun Lueke; Hirsch, Fred R.] Univ Colorado, Div Med Oncol, Anschutz Med Campus, Aurora, CO USA; [Suda, Kenichi] Kindai Univ, Fac Med, Dept Surg, Div Thorac Surg, Osaka, Japan; [Ren, Shengxiang] Tongji Univ, Shanghai Pulm Hosp, Shanghai, Peoples R China; [Laszlo, Viktoria; Harko, Tunde; Megyesfalvi, Zsolt; Moldvay, Judit; Dome, Balazs; Lohinai, Zoltan] Natl Koranyi Inst Pulmonol, Budapest, Hungary; [Laszlo, Viktoria; Megyesfalvi, Zsolt; Dome, Balazs] Semmelweis Univ, Dept Thorac Surg, Budapest, Hungary; [Laszlo, Viktoria; Megyesfalvi, Zsolt; Dome, Balazs] Natl Inst Oncol, Budapest, Hungary; [Laszlo, Viktoria; Megyesfalvi, Zsolt; Dome, Balazs] Med Univ Vienna, Comprehens Canc Ctr, Dept Surg, Div Thorac Surg, Waehringer Guertel 18-20, A-1090 Vienna, Austria; [Hirsch, Fred R.] Mt Sinai Hlth Syst, Tisch Canc Inst, Ctr Thorac Oncol, New York, NY USA
推荐引用方式 GB/T 7714	Dora, David,Rivard, Christopher,Yu, Hui,et al. Neuroendocrine subtypes of small cell lung cancer differ in terms of immune microenvironment and checkpoint molecule distribution[J],2020,14(9):1947-1965.
APA	Dora, David.,Rivard, Christopher.,Yu, Hui.,Bunn, Paul.,Suda, Kenichi.,...&Lohinai, Zoltan.(2020).Neuroendocrine subtypes of small cell lung cancer differ in terms of immune microenvironment and checkpoint molecule distribution.MOLECULAR ONCOLOGY,14(9),1947-1965.
MLA	Dora, David,et al."Neuroendocrine subtypes of small cell lung cancer differ in terms of immune microenvironment and checkpoint molecule distribution".MOLECULAR ONCOLOGY 14.9(2020):1947-1965.