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基于免疫检查点抑制剂的疗法:口腔潜在恶性疾病的新策略。

ICI-based therapies: A new strategy for oral potentially malignant disorders.

作者信息

Wang Tianqing, Sun Silu, Zeng Xin, Li Jing

机构信息

State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Research Unit of Oral Carcinogenesis and Management, Chinese Academy of Medical Sciences, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan 610041, PR China.

State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Research Unit of Oral Carcinogenesis and Management, Chinese Academy of Medical Sciences, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan 610041, PR China.

出版信息

Oral Oncol. 2023 May;140:106388. doi: 10.1016/j.oraloncology.2023.106388. Epub 2023 Apr 11.

Abstract

Oral potentially malignant disorders (OPMDs) are linked with an escalated risk of developing cancers, particularly oral squamous cell carcinoma (OSCC). Since prevailing therapies cannot effectively forestall the exacerbation and recurrence of OPMDs, halting their malignant progression is paramount. The immune checkpoint serves as a cardinal regulator of the immune response and the primary cause of adaptive immunological resistance. Although the exact mechanism remains elusive, elevated expression of multiple immune checkpoints in OPMDs and OSCC relative to healthy oral mucosa has been ascertained. This review delves into the immunosuppressive microenvironment of OPMDs, the expression of diverse immune checkpoints such as programmed death receptor-1 (PD-1) and programmed death receptor-1 ligand (PD-L1) in OPMDs, and the potential application of corresponding inhibitors. In addition, synergistic strategies incorporating combined immune checkpoint inhibitors, such as cGAS-STING, costimulatory molecules, cancer vaccines, and hydrogels, are discussed to gain a more comprehensive understanding of the role and application of immune checkpoint inhibitors (ICIs) in oral carcinogenesis.

摘要

口腔潜在恶性疾病(OPMDs)与患癌风险升高有关,尤其是口腔鳞状细胞癌(OSCC)。由于现有治疗方法无法有效阻止OPMDs的恶化和复发,阻止其恶性进展至关重要。免疫检查点是免疫反应的主要调节因子,也是适应性免疫抵抗的主要原因。尽管确切机制尚不清楚,但已确定与健康口腔黏膜相比,OPMDs和OSCC中多种免疫检查点的表达升高。本综述深入探讨了OPMDs的免疫抑制微环境、OPMDs中多种免疫检查点如程序性死亡受体-1(PD-1)和程序性死亡受体-1配体(PD-L1)的表达,以及相应抑制剂的潜在应用。此外,还讨论了联合免疫检查点抑制剂的协同策略,如cGAS-STING、共刺激分子、癌症疫苗和水凝胶,以更全面地了解免疫检查点抑制剂(ICIs)在口腔癌发生中的作用和应用。

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