程序性细胞死亡受体1与细胞毒性T淋巴细胞相关抗原4联合阻断治疗胰腺癌的研究进展

秦文科; 魏孔源; 赵学安; 周文策; 张辉

doi:10.12449/JCH251233

程序性细胞死亡受体1与细胞毒性T淋巴细胞相关抗原4联合阻断治疗胰腺癌的研究进展

DOI: 10.12449/JCH251233

1.
兰州大学第二临床医学院，兰州 730000
2.
西安交通大学第一附属医院肝胆外科，西安 710000
3.
兰州大学第二医院普通外科，兰州 730000

基金项目:

国家自然科学基金 (82360510);

陇原青年创新创业人才（团队）项目 (212088725013);

兰州大学第二医院萃英科技创新计划项目 (CY2022-MS-A11)

利益冲突声明：本文不存在任何利益冲突。

作者贡献声明：秦文科、赵学安负责综述框架设计，文献检索与筛选，主体内容撰写；魏孔源参与收集数据，修改论文；张辉、周文策负责拟定写作思路，指导撰写文章并最后定稿。

详细信息

通信作者:
张辉， ery_huizhang@lzu.edu.cn （ORCID： 0009-0005-5854-1170）

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出版历程
- 收稿日期: 2025-05-06
- 录用日期: 2025-06-25
- 出版日期: 2025-12-25

Research advances in combined blockade therapy for programmed cell death-1 and cytotoxic T-lymphocyte-associated antigen 4 in pancreatic cancer

1.
The Second Clinical Medical School of Lanzhou University，Lanzhou 730000，China
2.
Department of Hepatobiliary Surgery，The First Affiliated Hospital of Xi’an Jiaotong University，Xi’an 710000，China
3.
Department of General Surgery，The Second Hospital of Lanzhou University，Lanzhou 730000，China

Research funding:

National Natural Science Foundation of China (82360510);

Longyuan Young Innovation and Entrepreneurship Talent （Team） Program (212088725013);

Cuiying Scientific and Technological Innovation Program of the Second Hospital of Lanzhou University (CY2022-MS-A11)

More Information

Corresponding author: ZHANG Hui， ery_huizhang@lzu.edu.cn （ORCID： 0009-0005-5854-1170）

摘要

摘要: 胰腺癌（PC）是恶性程度极高、预后极差的消化道肿瘤，传统治疗手段对延长患者生存期的效果有限。近年来，免疫检查点抑制剂在多种实体瘤中取得突破性进展，其中程序性细胞死亡受体1与细胞毒性T淋巴细胞相关抗原4作为关键免疫检查点靶点备受关注。尽管二者在PC中的单独应用疗效不太理想，但双重阻断策略展现出更大的治疗潜力。本文从PC免疫微环境出发，系统综述程序性细胞死亡受体1与细胞毒性T淋巴细胞相关抗原4的生物学特性及其单药应用现状，重点探讨双重靶向治疗在PC中的研究进展及面临的挑战，并对未来发展方向进行展望。
- 胰腺肿瘤 /
- 免疫检查点抑制剂 /
- 程序性细胞死亡受体1 /
- CTLA-4抗原
Abstract: Pancreatic cancer is a highly malignant tumor of the digestive system with an extremely poor prognosis， and traditional treatment methods have a limited effect in prolonging the survival time of patients. In recent years， ground-breaking advances have been achieved for immune checkpoint inhibitors （ICI） in a variety of solid tumors， among which programmed cell death-1 （PD-1） and cytotoxic T-lymphocyte-associated antigen 4 （CTLA-4） have attracted much attention as major immune checkpoint targets. Although single-agent treatment with PD-1 or CTLA-4 inhibitor has an unsatisfactory effect in PC， the strategy of dual blockade has shown greater therapeutic potential. Starting from the immune microenvironment of PC， this article systematically reviews the biological characteristics of PD-1 and CTLA-4 and the current status of their single-agent applications， discusses the research advances and challenges in dual-targeted therapy for PC， and proposes the prospects for future development in this field.
- Pancreatic Neoplasms /
- Immune Checkpoint Inhibitors /
- Programmed Cell Death 1 Receptor /
- CTLA-4 Antigen

HTML全文

注： MHC-Ⅱ，主要组织相容性复合体Ⅱ类分子；PD-L1，程序性细胞死亡配体1；CD80/86，B7-1共刺激分子/B7-2共刺激分子；TCR，T细胞受体；PD-1，程序性细胞死亡受体1；CTLA-4，细胞毒性T淋巴细胞相关抗原4。

图 1 PD-1/PD-L1 与 CTLA-4 介导的 T 细胞失活机制示意图

Figure 1. Schematic diagram of T-cell inactivation mediated by PD-1/PD-L1 and CTLA-4

下载: 全尺寸图片幻灯片

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