a Department of Pathophysiology , Third Military Medical University , Chongqing , PR China.
b Department of Cell Biology , Third Military Medical University , Chongqing , PR China.
Immunol Invest. 2019 Jul;48(5):466-479. doi: 10.1080/08820139.2019.1566356. Epub 2019 Jan 28.
Programmed death-1 (PD-1), a key immune checkpoint molecule, has been developed as an oncotherapy target for various carcinomas. However, treatment with anti-PD-1 elicited only a minimal effect in pancreatic ductal adenocarcinoma (PDAC). Subsequent studies revealed the existence of a subset of PD-1 T cells coexpressing CD38 and CD101, representing a fixed dysfunctional subpopulation that are not able to be rescued by anti-PD-1 immunotherapy. However, whether this subpopulation of PD-1 expressing CD8 T cells could be useful in predicting PDAC stage or prognosing survival is unknown. In this study, we used flow cytometry and immunofluorescence assay to analyze the expression of CD38 and CD101 in 183 clinical PDAC samples, including 84 of peripheral blood and 99 of surgical tissues. High coexpression of CD38/CD101 on peripheral PD-1CD8 T cells or tumor-infiltrating lymphocytes (TILs) was found to be most significantly correlated with Tumor/Node/Metastasis (T/N/M) classification and clinical stage, in contrast PD-1CD8 T cells could not correlate with T classification. CD38/CD101 co-repression on TILs also correlated with the poor survival in these PDAC patient samples. Our data suggest that CD38/CD101 might represent a more helpful biomarker than PD-1 alone for diagnosis and prognosis of PDAC.
程序性死亡受体-1（PD-1）是一种关键的免疫检查点分子，已被开发为各种癌的肿瘤治疗靶点。然而，抗 PD-1 治疗在胰腺导管腺癌（PDAC）中仅产生微小的效果。随后的研究表明，PD-1 T 细胞存在共表达 CD38 和 CD101 的亚群，代表了一种固定的功能失调亚群，不能通过抗 PD-1 免疫治疗来挽救。然而，这种 PD-1 表达 CD8 T 细胞亚群是否可用于预测 PDAC 分期或预测生存尚不清楚。在这项研究中，我们使用流式细胞术和免疫荧光分析来分析 183 例临床 PDAC 样本中 CD38 和 CD101 的表达，包括 84 例外周血和 99 例手术组织。外周 PD-1CD8 T 细胞或肿瘤浸润淋巴细胞（TILs）上 CD38/CD101 的高共表达与肿瘤/淋巴结/转移（T/N/M）分类和临床分期最显著相关，而 PD-1CD8 T 细胞与 T 分类无关。TILs 上 CD38/CD101 的共抑制也与这些 PDAC 患者样本的不良生存相关。我们的数据表明，CD38/CD101 可能比 PD-1 本身更能作为 PDAC 诊断和预后的有用生物标志物。
