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.
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