干旱区生态环境知识资源中心(Arid): Characterization of Tumor-Associated Macrophages and the Immune Microenvironment in Limited-Stage Neuroendocrine-High and -Low Small Cell Lung Cancer

Arid

DOI	10.3390/biology10060502
	Characterization of Tumor-Associated Macrophages and the Immune Microenvironment in Limited-Stage Neuroendocrine-High and -Low Small Cell Lung Cancer
	Dora, David; Rivard, Christopher; Yu, Hui; Pickard, Shivaun Lueke; Laszlo, Viktoria; Harko, Tunde; Megyesfalvi, Zsolt; Dinya, Elek; Gerdan, Csongor; Szegvari, Gabor; Hirsch, Fred R.; Dome, Balazs; Lohinai, Zoltan
通讯作者	Dome, B ; Lohinai, Z (corresponding author), Natl Koranyi Inst Pulmonol, Dept Tumor Biol, Piheno Ut 1, H-1121 Budapest, Hungary. ; Dome, B (corresponding author), Semmelweis Univ, Dept Thorac Surg, H-1122 Budapest, Hungary. ; Dome, B (corresponding author), Natl Inst Oncol, H-1122 Budapest, Hungary.
来源期刊	BIOLOGY-BASEL
EISSN	2079-7737
出版年	2021
卷号	10 期号:6
英文摘要	Simple Summary To date, the therapeutic strategy and guidelines in small cell lung cancer (SCLC) are based on cancer cell-related attributes with no biomarker used in the clinical practice. In the present study, using RNAseq and IHC, we aim to characterize in the frontline the latest biomarkers of tumor-associated macrophages (TAMs), myeloid-derived suppressor cells (MDSC) and related critical elements, regulating the anti-tumor immune response. Accordingly, we extensively evaluated the TME associations in primary tumors and matched lymph node metastases in different tumor compartments (stroma and tumor nests) and neuroendocrine (NE) subtypes in limited-stage SCLC. We show the RNA gene enrichment of the most critical molecular pathways based on the Gene Ontology (GO) iteration system using thorough bioinformatics analysis to identify new molecular targets in distinct NE subtypes. This study aims to characterize tumor-infiltrating macrophages (TAMs), myeloid-derived suppressor cells (MDSC), and the related molecular milieu regulating anti-tumor immunity in limited-stage neuroendocrine (NE)-high and NE-low small cell lung cancer. Primary tumors and matched lymph node (LN) metastases of 32 resected, early-stage SCLC patients were analyzed by immunohistochemistry (IHC) with antibodies against pan-macrophage marker CD68, M2-macrophage marker CD163, and MDSC marker CD33. Area-adjusted cell counting on TMAs showed that TAMs are the most abundant cell type in the TME, and their number in tumor nests exceeds the number of CD3 + T-cells (64% vs. 38% in NE-low and 71% vs. 18% in NE-high). Furthermore, the ratio of CD163-expressing M2-polarized TAMs in tumor nests was significantly higher in NE-low vs. NE-high tumors (70% vs. 31%). TAM density shows a strong positive correlation with CD45 and CD3 in tumor nests, but not in the stroma. fGSEA analysis on a targeted RNAseq oncological panel of 2560 genes showed that NE-high tumors exhibited increased enrichment in pathways related to cell proliferation, whereas in NE-low tumors, immune response pathways were significantly upregulated. Interestingly, we identified a subset of NE-high tumors representing an immune-oasis phenotype, but with a different gene expression profile compared to NE-low tumors. In contrast, we found that a limited subgroup of NE-low tumors is immune-deserted and express distinct cellular pathways from NE-high tumors. Furthermore, we identified potential molecular targets based on our expression data in NE-low and immune-oasis tumor subsets, including CD70, ANXA1, ITGB6, TP63, IFI27, YBX3 and CXCR2.
英文关键词	SCLC neuroendocrine subtype macrophage tumor microenvironment fGSEA
类型	Article
语种	英语
开放获取类型	Green Published, gold
收录类别	SCI-E
WOS记录号	WOS:000667865400001
WOS关键词	SUPPRESSOR-CELLS ; ANNEXIN A1 ; EXPRESSION ; METASTASIS ; CARCINOMA ; RESPONSES ; RECEPTOR ; CD4(+) ; OVEREXPRESSION ; INFILTRATION
WOS类目	Biology
WOS研究方向	Life Sciences & Biomedicine - Other Topics
资源类型	期刊论文
条目标识符	http://119.78.100.177/qdio/handle/2XILL650/349712
作者单位	[Dora, David] Semmelweis Univ, Fac Med, Dept Anat Histol & Embryol, H-1094 Budapest, Hungary; [Rivard, Christopher; Yu, Hui; Pickard, Shivaun Lueke; Hirsch, Fred R.] Univ Colorado, Div Med Oncol, Anschutz Med Campus, Aurora, CO 80045 USA; [Laszlo, Viktoria; Harko, Tunde; Megyesfalvi, Zsolt; Gerdan, Csongor; Szegvari, Gabor; Dome, Balazs; Lohinai, Zoltan] Natl Koranyi Inst Pulmonol, Dept Tumor Biol, Piheno Ut 1, H-1121 Budapest, Hungary; [Laszlo, Viktoria; Megyesfalvi, Zsolt; Dome, Balazs] Semmelweis Univ, Dept Thorac Surg, H-1122 Budapest, Hungary; [Laszlo, Viktoria; Megyesfalvi, Zsolt; Dome, Balazs] Natl Inst Oncol, H-1122 Budapest, Hungary; [Laszlo, Viktoria; Megyesfalvi, Zsolt; Dome, Balazs] Med Univ Vienna, Comprehens Canc Ctr, Dept Surg, Div Thorac Surg, A-1090 Vienna, Austria; [Dinya, Elek] Semmelweis Univ, Fac Publ Serv, Inst Digital Hlth Sci, H-1094 Budapest, Hungary; [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. Characterization of Tumor-Associated Macrophages and the Immune Microenvironment in Limited-Stage Neuroendocrine-High and -Low Small Cell Lung Cancer[J],2021,10(6).
APA	Dora, David.,Rivard, Christopher.,Yu, Hui.,Pickard, Shivaun Lueke.,Laszlo, Viktoria.,...&Lohinai, Zoltan.(2021).Characterization of Tumor-Associated Macrophages and the Immune Microenvironment in Limited-Stage Neuroendocrine-High and -Low Small Cell Lung Cancer.BIOLOGY-BASEL,10(6).
MLA	Dora, David,et al."Characterization of Tumor-Associated Macrophages and the Immune Microenvironment in Limited-Stage Neuroendocrine-High and -Low Small Cell Lung Cancer".BIOLOGY-BASEL 10.6(2021).