胃癌患者外周血T细胞免疫球蛋白黏蛋白-3的表达及临床意义

doi:10.3877/cma.j.issn.1674-0785.2021.08.012

目的

探讨胃癌患者外周血T细胞T细胞免疫球蛋白黏蛋白-3（Tim-3）的表达及临床意义。

方法

收集2019年5月至2020年4月郑州大学第五附属医院45例胃癌患者的外周静脉血，同时收集23名健康人外周静脉血。流式细胞术检测45例胃癌患者及23名健康人外周血中Tim-3的表达，检测胃癌患者外周血Tim-3阳性及Tim-3阴性T细胞早期凋亡分子和内因子的表达水平，分析胃癌患者Tim-3表达与临床病理参数及幽门螺杆菌感染情况的关系。

结果

与健康志愿者比较，Tim-3在胃癌患者外周血T细胞中表达水平较高［（13.349±3.025）% vs （5.520±1.771）%，P＜0.001］。Tim-3⁺T细胞相比Tim-3^-T细胞分泌γ干扰素（INF-γ）能力减弱［（16.395±2.568）% vs （27.150±3.113）%，P＜0.001］，凋亡增多［（24.127±3.822）% vs（11.259±2.520）%，P＜0.001］。相比分期为Ⅰ~Ⅱ期的胃癌患者，分期为Ⅲ~Ⅳ期的患者外周血T细胞Tim-3表达水平明显升高［（14.463±2.951）% vs （11.515±2.175），P=0.001］；外周血T细胞Tim-3的表达与幽门螺杆菌感染无明显相关（P＞0.05）。

结论

胃癌患者T细胞中Tim-3高表达，导致T细胞功能耗竭，晚期胃癌患者Tim-3表达水平更高，可作为胃癌的有效治疗靶点。

关键词: 胃癌, T细胞免疫球蛋白黏蛋白-3, T细胞, 免疫检查点

Objective

To evaluate the clinical significance of expression of T cell immunoglobulin and mucin-domain-containing molecule-3 (Tim-3) in peripheral blood T cells of patients with gastric cancer.

Methods

Peripheral blood samples were collected from 45 patients with gastric cancer in the Fifth Affiliated Hospital of Zhengzhou University from May 2019 to April 2020. Peripheral blood samples from 23 healthy volunteers were also collected during the same time period. The expressions of Tim-3 in the peripheral blood samples of gastric cancer patients and healthy volunteers were detected by flow cytometry. Early apoptotic signaling molecules and intrinsic factors in peripheral blood with Tim-3⁺ T cells or Tim-3^- T cells were determined by flow cytometry. Also, the correlation between Tim-3 T cell expression with pathological parameters and Helicobacter pylori infection status was investigated.

Results

Compared with healthy volunteers, Tim-3 expression in T cells was higher in peripheral blood of gastric cancer patients [(13.349±3.025)% vs (5.520±1.771)%, P＜0.001]. Compared with Tim-3^- T cells, Tim-3⁺ T cells had less secreted interferon-γ [(16.395±2.568]% vs (27.150±3.113)%, P＜0.001] and increased apoptosis [(24.127±3.822)% vs (11.259±2.520)%, P＜0.001]. Compared with patients with stage Ⅰ/Ⅱ gastric cancer, the expression level of Tim-3 in peripheral blood T cells of patients with stage Ⅲ/Ⅳ gastric cancer was significantly higher [(14.463±2.951)% vs (11.515±2.175), P=0.001], but the expression of Tim-3 in peripheral blood T cells was not significant associated with Helicobacter pylori infection (P＞0.05).

Conclusion

Patients with gastric cancer have higher Tim-3 expression, which can induce T cell dysfunction. And the expression level of Tim-3 in advanced gastric cancer is even higher, suggesting that Tim-3 may serve as a potential therapeutic target for gastric cancer.

Key words: Gastric cancer, T cell immunoglobulin and mucin-domain-containing molecule-3, T cells, Immune checkpoint

图1 T细胞免疫球蛋白黏蛋白（Tim）-3在胃癌患者及健康志愿者外周血T细胞表面的表达情况图a为胃癌患者流式图；图b为健康志愿者流式图

图2 胃癌患者外周血T细胞干扰素（IFN）-γ分泌情况。左象限为Tim-3^-细胞群，其中，左上象限为IFN-γ⁺的Tim-3^-T细胞，左下象限为IFN-γ^-的Tim-3^-T细胞；右象限为Tim-3⁺细胞群，其中，右上象限为IFN-γ⁺的Tim-3⁺T细胞，右下象限为IFN-γ^-的Tim-3⁺T细胞注：Tim-3为T细胞免疫球蛋白黏蛋白-3

图3 胃癌患者外周血T细胞凋亡情况。左象限为Tim-3^-细胞群，其中，左上象限为Annexin Ⅴ⁺的Tim-3^-T细胞，左下象限为Annexin Ⅴ^-的Tim-3^-T细胞；右象限为Tim-3⁺细胞群，其中，右上象限为Annexin Ⅴ⁺的Tim-3⁺T细胞，右下象限为Annexin Ⅴ^-的Tim-3⁺T细胞注：Tim-3为T细胞免疫球蛋白黏蛋白-3

表1 胃癌患者外周血T细胞T细胞免疫球蛋白黏蛋白（Tim）-3的表达与临床病理参数的关系（%，

x ˉ

±s）

项目	例数	Tim-3表达水平	t值	P值
性别			0.272	0.787
男	28	13.446±2.662
女	17	13.190±3.629
年龄（岁）			-0.038	0.970
≤50	14	13.375±2.529
＞50	31	13.338±3.264
分化程度			0.693	0.492
高中分化	30	13.572±3.049
低分化	15	12.905±3.031
临床分期			-3.566	0.001
Ⅰ~Ⅱ期	17	11.515±2.175
Ⅲ~Ⅳ期	28	14.463±2.951
幽门螺杆菌感染			11.807	0.078
有	27	13.998±3.391
无	18	12.376±2.106

表1 胃癌患者外周血T细胞T细胞免疫球蛋白黏蛋白（Tim）-3的表达与临床病理参数的关系（%，

x ˉ

±s）

项目	例数	Tim-3表达水平	t值	P值
性别			0.272	0.787
男	28	13.446±2.662
女	17	13.190±3.629
年龄（岁）			-0.038	0.970
≤50	14	13.375±2.529
＞50	31	13.338±3.264
分化程度			0.693	0.492
高中分化	30	13.572±3.049
低分化	15	12.905±3.031
临床分期			-3.566	0.001
Ⅰ~Ⅱ期	17	11.515±2.175
Ⅲ~Ⅳ期	28	14.463±2.951
幽门螺杆菌感染			11.807	0.078
有	27	13.998±3.391
无	18	12.376±2.106

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Clinical significance of expression of T cell immunoglobulin and mucin-domain-containing molecule-3 in peripheral blood T cells of patients with gastric cancer

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Clinical significance of expression of T cell immunoglobulin and mucin-domain-containing molecule-3 in peripheral blood T cells of patients with gastric cancer