Tufail Muhammad, Jiang Can-Hua, Li Ning
Department of Oral and Maxillofacial Surgery, Center of Stomatology, Xiangya Hospital, Central South University, Changsha, China.
Institute of Oral Precancerous Lesions, Central South University, Changsha, China.
Signal Transduct Target Ther. 2025 Jul 31;10(1):227. doi: 10.1038/s41392-025-02280-1.
Immune evasion represents a significant challenge in oncology. It allows tumors to evade immune surveillance and destruction, thereby complicating therapeutic interventions and contributing to suboptimal patient outcomes. This review addresses the critical need to understand how cancers evade immune surveillance. It aims to provide a comprehensive overview of strategies of tumors to escape immune detection by examining tumor-induced immune suppression, immune checkpoint regulation, and genetic and epigenetic influences. Moreover, it explores the dynamic role of the tumor microenvironment (TME) in fostering immune resistance and highlights the impact of metabolic reprogramming on immune suppression. Additionally, this review focuses on how tumor heterogeneity influences immune evasion and discusses the limitations of current immunotherapies. The role of key signaling pathways, including programmed cell death protein 1/programmed cell death ligand 1 (PD-1/PD-L1), cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4), transforming growth factor-β (TGF-β), nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), and cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) is analyzed to elucidate their contributions to immune escape. Emphasizing the complexities of immune evasion, this review underscores the importance of personalized approaches and the integration of multi-omics data to combat therapeutic resistance. Furthermore, it discusses novel and emerging therapeutic strategies, such as bispecific antibodies, oncolytic viruses, and nanotechnology-driven immunotherapies, showcasing innovative avenues in cancer treatment. The significance of this review lies in its potential to guide future research and innovations in immunotherapy, ultimately improving patient outcomes and advancing our understanding of cancer immunology.
免疫逃逸是肿瘤学中的一项重大挑战。它使肿瘤能够逃避免疫监视和破坏,从而使治疗干预变得复杂,并导致患者预后不佳。本综述阐述了理解癌症如何逃避免疫监视的迫切需求。其目的是通过研究肿瘤诱导的免疫抑制、免疫检查点调节以及遗传和表观遗传影响,全面概述肿瘤逃避免疫检测的策略。此外,它还探讨了肿瘤微环境(TME)在促进免疫抵抗中的动态作用,并强调了代谢重编程对免疫抑制的影响。此外,本综述关注肿瘤异质性如何影响免疫逃逸,并讨论了当前免疫疗法的局限性。分析了关键信号通路的作用,包括程序性细胞死亡蛋白1/程序性细胞死亡配体1(PD-1/PD-L1)、细胞毒性T淋巴细胞相关抗原4(CTLA-4)、转化生长因子-β(TGF-β)、活化B细胞核因子κB(NF-κB)以及环磷酸鸟苷-腺苷酸合成酶-干扰素基因刺激物(cGAS-STING),以阐明它们对免疫逃逸的贡献。本综述强调了免疫逃逸的复杂性,强调了个性化方法以及整合多组学数据以对抗治疗耐药性的重要性。此外,它还讨论了新型和新兴的治疗策略,如双特异性抗体、溶瘤病毒和纳米技术驱动的免疫疗法,展示了癌症治疗中的创新途径。本综述的意义在于其有可能指导免疫治疗的未来研究和创新,最终改善患者预后并增进我们对癌症免疫学的理解。