Zhang Pingxu, Zhan Yiyi
Tumor Hospital Affiliated to Xinjiang Medical University, Urumqi 830000, China.
Zhongguo Fei Ai Za Zhi. 2025 Mar 20;28(3):221-229. doi: 10.3779/j.issn.1009-3419.2025.102.08.
Despite the groundbreaking advances in cancer immunotherapy achieved by immune checkpoint inhibitors (ICIs), their efficacy remains limited by the immunosuppressive tumor microenvironment (TME). Yes-associated protein (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ), key effectors of the Hippo signaling pathway, play pivotal roles in tumor immune evasion. They directly regulate the expression of immune checkpoints, mediate the formation of an immunosuppressive microenvironment, inhibit T cell function, and interact with other signaling pathways to promote immune escape. Diverse strategies targeting YAP/TAZ have been developed, including direct inhibition, modulation of upstream regulators, and suppression of downstream target genes. Preclinical studies have demonstrated that combining YAP/TAZ inhibition with ICIs significantly enhances therapeutic efficacy across various tumor models. This review summarizes recent advances in understanding the role of YAP/TAZ in immune evasion within the TME and explores the potential of targeting this pathway to improve immunotherapy outcomes. Furthermore, it discusses the translational value of combination therapies based on YAP/TAZ inhibition, providing a theoretical framework and practical guidance for the development of innovative immunotherapeutic strategies and precision medicine approaches. .
尽管免疫检查点抑制剂（ICI）在癌症免疫治疗方面取得了突破性进展，但其疗效仍受免疫抑制性肿瘤微环境（TME）的限制。Yes相关蛋白（YAP）和具有PDZ结合基序的转录共激活因子（TAZ）是Hippo信号通路的关键效应因子，在肿瘤免疫逃逸中起关键作用。它们直接调节免疫检查点的表达，介导免疫抑制性微环境的形成，抑制T细胞功能，并与其他信号通路相互作用以促进免疫逃逸。已开发出多种针对YAP/TAZ的策略，包括直接抑制、调节上游调节因子和抑制下游靶基因。临床前研究表明，将YAP/TAZ抑制与ICI联合使用可显著提高各种肿瘤模型的治疗效果。本综述总结了在理解YAP/TAZ在TME内免疫逃逸中的作用方面的最新进展，并探讨了靶向该通路以改善免疫治疗结果的潜力。此外，还讨论了基于YAP/TAZ抑制的联合疗法的转化价值，为创新免疫治疗策略和精准医学方法的开发提供了理论框架和实践指导。
