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Identification and validation of an immunogenic subtype of gastric cancer with abundant intratumoural CD103+CD8+ T cells conferring favourable prognosis.
British Journal of Cancer ( IF 6.4 ) Pub Date : 2020-03-24 , DOI: 10.1038/s41416-020-0813-y
Ruochen Li 1 , Hao Liu 1 , Yifan Cao 1 , Jieti Wang 2 , Yifan Chen 3 , Yangyang Qi 3 , Kunpeng Lv 4 , Xin Liu 4 , Kuan Yu 1 , Chao Lin 1 , Heng Zhang 1 , Hongyong He 1 , He Li 1 , Lingli Chen 5 , Zhenbin Shen 1 , Jing Qin 1 , Weijuan Zhang 3 , Yihong Sun 1 , Jiejie Xu 4
Affiliation  

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.

中文翻译:

具有丰富的肿瘤内CD103 + CD8 + T细胞的胃癌免疫原性亚型的鉴定和验证,预后良好。

背景技术肿瘤内的CD103 + CD8 + T细胞与多种恶性肿瘤的延长生存期有关。然而,CD103 + CD8 + T细胞在胃癌中的临床意义尚待探索。方法收集并分析中山医院胃癌组织和Gene Expression Omnibus数据。进行免疫组织化学和流式细胞仪检测CD103 + CD8 + T细胞的数量和表型特征。利用基于新鲜肿瘤组织的体外研究评估了程序性细胞死亡蛋白-1(PD-1)阻断对CD103 + CD8 + T细胞的影响。结果与胃癌中的总CD8 + T细胞相比,CD103 + CD8 + T细胞可预测更高的总生存期并提供更好的预后能力。高CD103 + CD8 + T细胞浸润的患者也从辅助化疗中获益更多。流式细胞仪分析表明,CD103 + CD8 + T细胞发挥了卓越的抗肿瘤作用,具有更强的保留能力和细胞毒性。此外,一项体外研究表明,PD-1阻断后,CD103 + CD8 + T细胞比CD103-CD8 + T细胞功能更强。结论CD103 + CD8 + 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。增加肿瘤内CD103 + CD8 + T细胞频率的努力可能是胃癌的一种新的治疗策略。一项体外研究表明,PD-1阻断后,CD103 + CD8 + T细胞比CD103-CD8 + T细胞功能更强。结论CD103 + CD8 + 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。增加肿瘤内CD103 + CD8 + T细胞频率的努力可能是胃癌的一种新的治疗策略。一项体外研究表明,PD-1阻断后,CD103 + CD8 + T细胞比CD103-CD8 + T细胞功能更强。结论CD103 + CD8 + 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。增加肿瘤内CD103 + CD8 + T细胞频率的努力可能是胃癌的一种新的治疗策略。
更新日期:2020-04-24
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