Identification and validation of an immunogenic subtype of gastric cancer with abundant intratumoural CD103+CD8+ T cells conferring favourable prognosis
Identification and validation of an immunogenic subtype of gastric cancer with abundant intratumoural CD103+CD8+ T cells conferring favourable prognosis
复制标题
胃癌免疫原性亚型的鉴定和验证，具有丰富的瘤内 CD103 CD8 T 细胞，可赋予良好的预后
DOI：
10.1038/s41416-020-0813-y
复制
发表时间：
2020-03-24
影响因子：
8.8
通讯作者：
Xu, Jiejie
中科院分区：
文献类型：
--
作者：
Li, Ruochen;Liu, Hao;Xu, Jiejie
背景
肿瘤内CD 103 + CD 8 + T细胞与几种恶性肿瘤的生存期延长有关。然而，CD 103 + CD 8 + T细胞在胃癌中的临床意义尚不清楚。
方法
收集中山医院胃癌组织和基因表达数据库的数据进行分析。免疫组化和流式细胞术检测CD 103 + CD 8 + T细胞的数量和表型特征。使用基于新鲜肿瘤组织的体外研究评价程序性细胞死亡蛋白-1（PD-1）阻断对CD 103 + CD 8 + T细胞的影响。
结果
在胃癌中，CD 103 + CD 8 + T细胞预测上级总生存率，并提供比总CD 8 + T细胞更好的预后能力。高CD 103 + CD 8 + T细胞浸润的患者也从辅助化疗中获益更多。流式细胞仪分析显示，CD 103 + CD 8 + T细胞具有较强的滞留能力和细胞毒性，显示出较好的上级抗肿瘤作用。此外，体外研究表明，在PD-1阻断后，CD 103 + CD 8 + T细胞比CD 103-CD 8 + T细胞功能恢复得更多。
结论
CD 103 + CD 8 + T细胞可能是预测胃癌患者预后和治疗效果的有用标志物。提高肿瘤内CD 103 + CD 8 + T细胞频率可能是胃癌治疗的新策略。
Background
Intratumoural CD103+CD8+ T cells have been linked to prolonged survival in several malignancies. However, the clinical significance of CD103+CD8+ T cells in gastric cancer remains unexplored.
Methods
Gastric cancer tissues from Zhongshan Hospital and data from Gene Expression Omnibus were obtained and analysed. Immunohistochemistry and flow cytometry were performed to detect the number and phenotypical characteristics of CD103+CD8+ T cells. The effect of programmed cell death protein-1 (PD-1) blockade on CD103+CD8+ T cells was evaluated with the use of an in vitro study based on fresh tumour tissues.
Results
CD103+CD8+ T cells predicted superior overall survival and provided better prognostic power than total CD8+ T cells in gastric cancer. Patients with high CD103+CD8+ T cell infiltration also gained more benefit from adjuvant chemotherapy. Flow cytometry analysis showed that CD103+CD8+ T cells exerted superior anti-tumour effects with stronger retention capacity and cytotoxicity. Moreover, an in vitro study showed that CD103+CD8+ T cells were more functionally restored after PD-1 blockade than CD103-CD8+ T cells.
Conclusions
CD103+CD8+ T cells might be a useful marker to predict prognosis and therapeutic efficacy for gastric cancer patients. Efforts to increase intratumoural CD103+CD8+ T cell frequency might be a novel therapeutic strategy in gastric cancer.