Clinical significance of CD8+ T cell immunoreceptor with Ig and ITIM domains+ in locally advanced gastric cancer treated with SOX regimen after D2 gastrectomy

Clinical significance of CD8+ T cell immunoreceptor with Ig and ITIM domains+ in locally advanced gastric cancer treated with SOX regimen after D2 gastrectomy
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具有Ig和ITIM结构域的CD8( ) T细胞免疫受体( )在D2胃切除术后SOX方案治疗局部进展期胃癌中的临床意义

DOI:
10.1080/2162402x.2019.1593807
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发表时间:
2019-06-03
期刊:
影响因子:
7.2
通讯作者:
Wang, Xuehao
Wang, Xuehao
中科院分区:
医学2区
文献类型:
--
作者:
Tang, Weiwei;Pan, Xiongxiong;Wang, Xuehao

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胃癌(GC)的发生和进展与肿瘤免疫逃逸显著相关。具有IG和ITIM结构域的T细胞免疫受体(TIGIT)抑制T细胞应答并且与人类癌症和T细胞耗竭表型相关,但其在癌症中的作用仍不清楚。采用组织化学法检测441例人胃癌标本中TIGIT和程序性细胞死亡蛋白(PD)-1水平。我们使用流式细胞术评估23例接受D2胃切除术和S-1加奥沙利铂(SOX)方案的GC患者的TIGIT(+)构成CD 8(+)T细胞的百分比。我们研究了SOX方案和TIGIT功能性抗体对CD 8肿瘤浸润淋巴细胞(TIL)的影响。结果显示,PD-1和TIGIT在GC中显著过表达,并预测较差的结局,与生物信息学分析一致。在D2胃切除术后的患者中观察到CD 8(+)TIGIT(+)细胞百分比显著降低(术前vs术后,38 +/- 8.7% vs. 26.7% +/-5.2%,p
Gastric cancer (GC) development and progression is significantly associated with tumour immune escape. T cell immunoreceptor with Ig and ITIM domains (TIGIT) inhibits T-cell responses and is associated with human cancers and T cell exhaustion phenotypes, but its role in cancers remains unclear. TIGIT and programmed cell death protein (PD)-1 levels were detected in 441 human GC specimens using histochemistry. We used flow cytometry to evaluate percentage of TIGIT(+) constituting CD8(+) T cells of 23 patients with GC who underwent D2 gastrectomy and the S-1 plus oxaliplatin (SOX) regimen. We investigated the influence of SOX regimen and TIGIT functional antibody on CD8 tumour-infiltrating lymphocytes (TILs). Results showed that PD-1 and TIGIT were significantly over expressed in GC and predicted poorer outcome, agreeing with bioinformatics analysis. Significantly reduced percentages of CD8(+) TIGIT(+) cells were observed in patients after D2 gastrectomy (pre- vs post-surgery, 38 +/- 8.7% vs. 26.7% +/- 5.2%, p