编程性细胞死亡蛋白-1（PD-1），亦称为CD279，由PDCD1基因编码，并在免疫细胞表面上持续表达。作为受体和免疫检查点，PD-1能够与肿瘤细胞中的程序性死亡配体-1/程序性死亡配体-2（PD-L1/PD-L2）结合，导致肿瘤免疫逃逸。抗PD-1和抗PD-L1是肿瘤免疫疗法中的重要组成部分。最近的研究提出，PD-1也以内在变体（iPD-1）的形式表达在癌细胞中，在恶性进展中起重要作用。然而，与免疫细胞上表达的PD-1相比，iPD-1受到了较少的关注，尽管在完全阐明机制以实现肿瘤免疫治疗的最佳反应方面存在未满足的医学需求。iPD-1在非小细胞肺癌（NSCLC）和结肠癌中抑制肿瘤发生，然而在黑色素瘤、肝细胞癌（HCC）、胰腺导管腺癌（PDAC）、甲状腺癌（TC）、胶质母细胞瘤（GBM）和三阴性乳腺癌（TNBC）中促进肿瘤发生。在本综述中，我们重点关注iPD-1在肿瘤发生和发展中的作用及其分子机制。我们还深入讨论了基于尼伐霉素的常见肿瘤治疗的联合疗法。iPD-1可以解释抗PD-1治疗的不同疗效，并为联合抗肿瘤方法的使用提供关键信息。版权所有 © 2023 作者。由Elsevier Masson SAS出版。保留所有权利。

Programmed cell death protein-1 (PD-1), also called CD279, is coded by the PDCD1 gene and is constitutively expressed on the surface of immune cells. As a receptor and immune checkpoint, PD-1 can bind to programmed death ligand-1/programmed death ligand-2 (PD-L1/PD-L2) in tumor cells, leading to tumor immune evasion. Anti-PD-1 and anti-PD-L1 are important components in tumor immune therapy. PD-1 is also expressed as an intrinsic variant (iPD-1) in cancer cells where it plays important roles in malignant progression as proposed by recent studies. However, iPD-1 has received much less attention compared to PD-1 expressed on immune cells although there is an unmet medical need for fully elucidating the mechanisms of actions to achieve the best response in tumor immunotherapy. iPD-1 suppresses tumorigenesis in non-small cell lung cancer (NSCLC) and colon cancer, whereas it promotes tumorigenesis in melanoma, hepatocellular carcinoma (HCC), pancreatic ductal adenocarcinoma (PDAC), thyroid cancer (TC), glioblastoma (GBM), and triple-negative breast cancer (TNBC). In this review, we focus on the role of iPD-1 in tumorigenesis and development and its molecular mechanisms. We also deeply discuss nivolumab-based combined therapy in common tumor therapy. iPD-1 may explain the different therapeutic effects of anti-PD-1 treatment and provide critical information for use in combined anti-tumor approaches.Copyright © 2023 The Authors. Published by Elsevier Masson SAS.. All rights reserved.