Department of General Surgery, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, 310000, China.
Sci Rep. 2017 Aug 10;7(1):7848. doi: 10.1038/s41598-017-08479-9.
Pancreatic cancer is one of the most aggressive malignancies and has a highly immunosuppressive tumour microenvironment. Immune checkpoint blockade has led to remarkable and durable objective responses in a number of malignancies and antibody-based strategies targeting programmed cell death protein 1 (PD-1) are showing promise where traditional modalities of surgery, radiotherapy, and chemotherapy have failed. In this study, we examined the clinical value of PD-1 protein expression by CD8+ peripheral T lymphocytes or tumour-infiltrating T lymphocytes (TILs) in pancreatic ductal adenocarcinoma (PDAC). Expression of PD-1 protein on CD8+ TILs correlated with overall survival and clinicopathological characteristics such as clinical stage, N classification, and M classification. Similar findings were observed for the expression of PD-1 protein on peripheral CD8+ T cells, whereas its expression on peripheral CD4+ T cells showed no significance. Comparison of the levels of PD-1 protein expressed by peripheral CD8+ T cells before and 4 weeks after surgery indicated that preoperative and postoperative status of peripheral PD-1 expression was unchanged. Our findings showed that PD-1 protein expressed by peripheral or tumour-infiltrated CD8+ T cells was a promising biomarker for diagnosis and prognosis in PDAC and might help guide future immunotherapies.
胰腺癌是最具侵袭性的恶性肿瘤之一，具有高度免疫抑制性的肿瘤微环境。免疫检查点阻断在多种恶性肿瘤中导致了显著和持久的客观反应，针对程序性细胞死亡蛋白 1（PD-1）的抗体策略在传统的手术、放疗和化疗失败的情况下显示出了希望。在这项研究中，我们研究了 PD-1 蛋白在胰腺导管腺癌（PDAC）中 CD8+外周 T 淋巴细胞或肿瘤浸润 T 淋巴细胞（TIL）中的表达的临床价值。CD8+TIL 上 PD-1 蛋白的表达与总生存期以及临床分期、N 分类和 M 分类等临床病理特征相关。在外周 CD8+T 细胞上 PD-1 蛋白的表达也观察到了类似的发现，而在外周 CD4+T 细胞上 PD-1 蛋白的表达则没有意义。比较手术前后外周 CD8+T 细胞表达的 PD-1 蛋白水平表明，外周 PD-1 表达的术前和术后状态没有改变。我们的研究结果表明，外周或肿瘤浸润的 CD8+T 细胞表达的 PD-1 蛋白是 PDAC 诊断和预后的有前途的生物标志物，可能有助于指导未来的免疫治疗。
