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胃癌淋巴细胞亚群中KLRG1和TIGIT的表达及意义

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目的 探讨胃癌患者外周血、癌及癌旁组织淋巴细胞中CD4+T、CD8+T、NK及NKT细胞上杀伤细胞凝集素样受体G1(Killer cell lectin-like receptor G1,KLRG1)、T细胞免疫球蛋白和ITIM结构域蛋白(T cell immunoglobulin and ITIM domains,TIGIT)的表达水平差异,并探讨其与临床特征、预后及免疫疗效的关系.方法 纳入2022年1月-2023年12月新疆医科大学附属肿瘤医院行手术的初治胃癌患者,留取癌组织36例,癌旁组织31例,采集15例患者治疗前的外周血,通过流式细胞术检测外周血、癌和癌旁组织淋巴细胞中CD4+T、CD8+T、NK及NKT细胞上KLRG1和TIGIT的表达,并分析其表达与临床特征的关系;利用Kaplan-Meier Plotter在线数据库分析KLRG1和TIGTI在胃癌中的预后价值;从TCIA数据库中获得免疫表型分数(IPS)探讨KLRG1和TIGIT表达对免疫治疗的敏感性.结果 (1)在GC癌组织中KLRG1+CD8+T细胞、KLRG1+NKT 细胞、TIGIT+CD8+T 细胞、TIGIT+CD4+T 细胞、TIGIT+NKT、TIGIT+NK、KLRG1+TIGIT+CD8+T细胞、KLRG1+TIGIT+CD4+T细胞表达高于癌旁组织,差异均具有统计学意义(P<0.05).(2)在外周血中KLRG1+CD8+T细胞、KLRG1+NKT细胞表达高于癌组织,差异均具有统计学意义(P<0.05),而TIGIT+CD4+T细胞、TIGIT+CD8+T细胞外周血中的表达低于癌组织,差异均具有统计学意义(P<0.05).(3)KLRG1+CD4+T细胞、KLRG1+CD8+T细胞、KLRG1+NKT细胞与肿瘤指标CA199呈正相关(r分别为0.37、0.45、0.40,P<0.05),KLRG1+NKT 细胞与 CA125 呈正相关(r=0.33,P<0.05).(4)KLRG1 高表达组患者的中位总生存时间、中位首次进展生存时间、中位进展后生存时间均短于KLRG 1低表达组,差异均有统计学意义(P<0.05).(5)在预测免疫治疗疗效方面,KLRG1和TIGIT高表达组对抗PD-1治疗以及抗PD-1和抗CTLA4联合治疗的反应优于低表达组(P<0.001).结论 KLRG1和TIGIT在胃癌组织中高表达,且KLRG高表达与胃癌的不良预后有关,KLRG1和TIGIT的表达可能有助于预测胃癌患者免疫治疗疗效.
Expression and significance of killer cell lectin-like receptor G1(KLRG1)and T cell immunoglobulin and ITIM domains(TIGIT)
Objective To investigate the difference of killer cell lectin-like receptor G1(KLRG1)and T cell immunoglobulin and ITIM domains(TIGIT)expression levels on CD4+T,CD8+T,NK and NKT cells in peripheral blood,cancer and adjacent tissue lymphocytes of the patients with gastric cancer,and to explore the relationship between KLRG1 and TIGIT expression levels and clinical features,prognosis and immune efficacy.Methods Primary gastric cancer patients who were feasible for surgery in the hospital from Janu-ary 2022 to December 2023 were included,36 cases of cancerous tissues and 31 cases of paracancerous tis-sues were retained,and peripheral blood was collected from 15 cases before the treatment.The expres-sions of KLRG1 and TIGIT on CD4+T,CD8+T,NK and NKT cells in PBMCs,tumor and adjacent TILs were detected by flow cytometry.The relationship between its expression and clinical features was ana-lyzed.The prognostic value of KLRG1 and TIGTI in gastric cancer used by Kaplan-Meier plotter online database.Immunophenotypic scores were obtained from the TCIA database to study the sensitivity of KLRG1 and TIGIT expression to immunotherapy.Results(1)The expression of KLRG1+CD8+T cells,KLRG1+NKT cells,TIGIT+CD8+T cells,TIGIT+CD4+T cells,TIGIT+NKT,TIGIT+NK,KLRG1+TIGIT+CD8+T cells and KLRG1+TIGIT+CD4+T cells in tumor were significantly higher than that of ad-jacent tissues(P<0.05).(2)The expression of KLRG1+CD8+T cells and KLRG1+NKT cells in periph-eral blood was significantly higher than that in cancer tissues(P<0.05).However,the expression of TIGIT CD4+T and TIGIT+CD8+T cells in peripheral blood was lower than that in cancer tissues(P<0.05).(3)KLRG1+CD4+T cells,KLRG1+CD8+T cells and KLRG1+NKT cells were positively correlated withCA199(r=0.37,0.45,0.40,P<0.05)and KLRG1+NKT cells were also positively correlated with CA125(r=0.33,P<0.05).(4)The median overall survival time,median first progression survival time and median post-progression survival time of the patients with high KLRG1 expression group were signifi-cantly shorter than those with low KLRG1 expression group(P<0.05).(5)In predicting the efficacy of immunotherapy,the high KLRG1 and TIGIT expression group responded better than the low expression group to anti-PD-1 therapy and the combination of anti-PD-1 and anti-CTLA4 therapy(P<0.001).Con-clusion KLRG1 and TIGIT are highly expressed in gastric cancer tissues.The high expression of KLRG1 in gastric cancer is related to the poor prognosis of gastric cancer.The expression of KLRG1 and TIGIT can effectively predict the immunotherapy response in gastric cancer patients.

gastric cancerkiller cell lectin-like receptor G1(KLRG1)T cell immunoglobulin and ITIM domains(TIGIT)T cellsclinical featuresprognosis

蒲艳霞、范佩文、冯亚宁、王海江、王若峥

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新疆医科大学第三临床医学院新疆肿瘤学重点实验室

中国医学科学院肿瘤免疫与放疗研究重点实验室

新疆放射治疗临床重点专科

新疆肿瘤放射治疗临床研究培育中心,乌鲁木齐 830011

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胃癌 KLRG1 TIGIT T细胞 临床特征 预后

2024

新疆医科大学学报
新疆医科大学

新疆医科大学学报

CSTPCD
影响因子:0.76
ISSN:1009-5551
年,卷(期):2024.47(12)