國家衛生研究院 NHRI:Item 3990099045/12284

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Please use this identifier to cite or link to this item: http://ir.nhri.org.tw/handle/3990099045/12284

Title:	Recapitulation of inflammatory and immune-evasive subtypes of oral cancer cells in immunodeficient mice
Authors:	Lin, SF;Ko, YC;Wang, FH;Su, SY;Chen, YL;Lai, TY;Liu, YH;Lin, CY;Hsu, SC
Contributors:	National Institute of Cancer Research;National Institute of Infectious Diseases and Vaccinology
Abstract:	Background: Prior study stratified Taiwanese oral cancer specimens (n = 40) and cell lines (n = 7) into three distinct molecular subtypes, namely classical (CL), mesenchymal (MS), and basal (BA). In a cell line derived xenograft (CDX) model, we observed MS grew at least 10-fold slower than CL did in immunodeficient mice. By using RNA-seq to portrait the transcriptomes of human tumor and mouse stroma simultaneously, contribution of mouse innate immunity in restricting the growth of human oral cancer cells was assessed. Methods: A half millions of mycoplasma-free OC3 (MS) or TW2.6 (CL) cells with matrigel were subcutaneously implanted into the flank of 10 to 16 weeks old NOG (NOD/SCID/Il2rgtm). RNAs of CDX tissues from OC3-NOG (n = 7) and TW2.6-NOG (n = 5) were extracted and subjected to stranded mRNA sequencing. Clean reads were aligned to GRCh38 (human) and GRCm38 (mouse), respectively, followed by identifying differentially expressed genes and gene set enrichment analysis. Results: Up-regulation of signature genes for dendritic cells and macrophages and enrichment of innate immunity, including Tnfa-Nfkb signaling, interferon alpha response, interferon gamma response and inflammation were detected in OC3- but not in TW2.6-CDXs. These results suggested that OC3 (MS) was more immunogenic than TW2.6 (CL), which is reminiscent of the inflammatory MS (IMS) subtype of head and neck cancer recently described by Keck et al (n = 938, Clin Cancer Res 2015, 21: p870. PMID: 25492084). Conclusions: By RNA-seq/xenome analysis of CDXs, we provide evidence that compared to CL, MS subtype of oral cancer cells elicited a stronger innate immunity in NOG mouse. Alternatively, CL subtype might have evolved as a prototype with superiority in immune escape.
Date:	2019-05
Relation:	Journal of Clinical Oncology. 2019 May;37(15, Suppl. S):Abstract number e14199.
Link to:	http://dx.doi.org/10.1200/JCO.2019.37.15_suppl.e14199
JIF/Ranking 2023:	http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=0732-183X&DestApp=IC2JCR
Cited Times(WOS):	https://www.webofscience.com/wos/woscc/full-record/WOS:000487345800556
Appears in Collections:	[Su-Fang Lin] Conference Papers/Meeting Abstract [Shu-Ching Hsu] Conference Papers/Meeting Abstract [Chung-Yen Lin(1999-2005)] Conference Papers/Meeting Abstract

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