具核梭杆菌对食管鳞状细胞癌组织CD8^(+)T细胞浸润及预后的影响  被引量:2

Effects of Fusobacterium nucleatum on CD8^(+)T cell infiltration in esophageal squamous cell carcinoma tissue and prognosis of patients

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作  者:张家豪 刘怡文[2] 何珂瑶 张哲源 李若楠 龙情柔 孙蔚[2] 孔金玉 杨海军[3] 周福有 ZHANG Jiahao;LIU Yiwen;HE Keyao;ZHANG Zheyuan;LI Ruonan;LONG Qingrou;SUN Wei;KONG Jinyu;YANG Haijun;ZHOU Fuyou(Department of Thoracic Surgery,the Third Affiliated Hospital,Xinxiang Medical University,Xinxiang,Henan 453003;College of Clinical Medicine,Henan University of Science and Technology,the First Affiliated Hospital,Henan University of Science and Technology,Henan Key Laboratory of Cancer Epigenetics,Henan Key Laboratory of Microbiome and Esophageal Cancer Prevention and Treatment,Luoyang,Henan 471003;Department of Pathology,Anyang Tumor Hospital,Anyang,Henan 455000;Department of Thoracic Surgery,Anyang Tumor Hospital,Henan Provincial Key Laboratory of Precision Medicine for Prevention and Treatment of Esophageal Cancer,Anyang,Henan 455000)

机构地区:[1]新乡医学院第三附属医院胸外科,河南新乡453003 [2]河南科技大学临床医学院,河南科技大学第一附属医院,河南省肿瘤表观遗传重点实验室,河南省微生态与食管癌防治重点实验室,河南洛阳471003 [3]安阳市肿瘤医院病理科,河南安阳455000 [4]安阳市肿瘤医院胸外科,河南省食管癌精准防治医学重点实验室,河南安阳455000

出  处:《郑州大学学报(医学版)》2023年第5期593-598,共6页Journal of Zhengzhou University(Medical Sciences)

基  金:河南省科技攻关项目(202102310129,212102310670);河南省医学科技攻关省部共建项目(LHGJ20200583,LHGJ20200811,SBGJ202103099,SBGJ202103100);安阳市重大科技专项(ZDKJJH2020006,2022A02SF002)。

摘  要:目的:分析具核梭杆菌(Fn)对食管鳞状细胞癌(ESCC)组织CD8^(+)T细胞浸润及预后的影响,并探讨其可能机制。方法:采用Fn分别感染ESCC细胞(KYSE140、KYSE150)24、48及72 h,应用流式细胞术检测ESCC细胞中吲哚胺2,3-双加氧酶(IDO)的表达情况。建立人CD8^(+)T细胞与KYSE140或KYSE150共培养体系,并分为对照组、Fn组、IDO抑制剂(1μmol/L)组及Fn^(+)IDO抑制剂组,处理24、48、72 h后检测共培养体系中CD8^(+)T细胞的增殖情况。采用RNAscope及免疫组化染色法检测243例ESCC组织中Fn感染、IDO表达及CD8^(+)T细胞浸润情况,并分析三者的关联性。采用Kaplan-Meier生存曲线和Cox回归分析Fn感染对ESCC患者预后的影响。结果:Fn感染可诱导KYSE140、KYSE150细胞中IDO表达增高,且具有时间依赖性(P<0.05)。Fn感染可抑制共培养体系中CD8^(+)T细胞增殖,IDO抑制剂则促进增殖,二者联用有拮抗作用(P<0.05)。ESCC组织中Fn感染及IDO表达具有一致性(Kappa=0.713),而二者均与CD8^(+)T细胞浸润呈负关联(P<0.05)。Kaplan-Meier生存曲线显示,Fn感染患者预后较差(P<0.05)。Cox回归分析结果显示Fn感染的ESCC患者死亡风险增加(HR=1.880,95%CI为1.326~2.663)。结论:Fn可能通过诱导IDO高表达抑制CD8^(+)T细胞增殖,削弱机体抗肿瘤免疫反应,促进ESCC恶性进展。Aim:To analyze the effects of Fusobacterium nucleatum(Fn)on CD8^(+)T cell infiltration in esophageal squamous cell carcinoma(ESCC)tissue and prognosis of ESCC patients,and to explore the possible mechanism.Methods:ESCC cells(KYSE140,KYSE150)were infected with Fn for 24,48 and 72 hours,and the expression of indoleamine 2,3-dioxygenase(IDO)in ESCC cells was detected by flow cytometry.The co-culture system of human CD8^(+)T cells with KYSE140 or KYSE150 was established and divided into control group,Fn group,IDO inhibitor(1μmol/L)group and Fn^(+)IDO inhibitor group,and after 24,48,72 hours,the proliferation of CD8^(+)T cells in the co-culture system was detected by flow cytometry.Fn infection,IDO expression and CD8^(+)T cell infiltration in 243 cases of ESCC tissue were detected by RNAscope and immunohistochemistry,and the association among the 3 factors was analyzed.Kaplan-Meier survival analysis and Cox regression were used to analyze the effects of Fn infection on the prognosis of ESCC patients.Results:Fn infection induced increased IDO expression in KYSE140 and KYSE150 cells in a time-dependent manner(P<0.05).Fn infection inhibited CD8^(+)T cell proliferation in co-culture system,while IDO inhibitor prompted the proliferation(P<0.05).Fn infection and IDO high expression in ESCC tissue were consistent(Kappa=0.713),and both of them were negatively associated with CD8^(+)T cell infiltration(P<0.05).The patients with Fn infection had worse prognosis(P<0.05).Fn infection increased the risk of death in ESCC patients(HR=1.880,95%CI was 1.326-2.663).Conclusion:Fn may inhibit the proliferation of CD8^(+)T cells by inducing IDO overexpression,weaken the anti-tumor immune response,and promote the malignant progression of ESCC.

关 键 词:食管鳞状细胞癌 具核梭杆菌 吲哚胺2 3-双加氧酶 CD8^(+)T细胞 预后 

分 类 号:R735.1[医药卫生—肿瘤]

 

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