重编程工程化自体 T 细胞以克服 Merkel 细胞癌患者的耐药性
Reprogramming engineered autologous T cells to overcome resistance in patients with Merkel cell carcinoma.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:The role of MHC molecules in cancer immunotherapy: Insights into tumor immune evasion and therapeutic strategies.
The role of MHC molecules in cancer immunotherapy: Insights into tumor immune evasion and therapeutic strategies.
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主要组织相容性复合体(MHC)分子作为免疫系统中抗原呈递的核心介质,通过向CD8和CD4 T细胞呈递抗原,在激活抗肿瘤免疫应答中发挥关键作用。然而,肿瘤细胞和肿瘤微环境(TME)中的免疫抑制细胞采用多维机制来失调MHC的表达和功能——包括表观遗传沉默、自噬降解以及干扰转录因子如NLRC5(针对MHC-I)和CIITA(针对MHC-II)。这些机制使免疫逃逸成为可能,并限制了癌症免疫治疗的疗效。此外,我们综述了基于MHC的治疗策略——如细胞因子治疗、TCR-T细胞治疗、免疫检查点抑制剂(ICI)联合治疗和肿瘤疫苗治疗——这些策略已被开发用于恢复MHC功能并克服免疫逃逸。更深入地理解肿瘤免疫中调控MHC分子的调节网络,将为开发精准有效的免疫治疗策略提供关键见解,最终改善癌症患者的临床结局。
Major histocompatibility complex (MHC) molecules, as core mediators of antigen presentation in the immune system, play pivotal roles in activating anti-tumor immune responses by presenting antigens to CD8 and CD4 T cells.
However, tumor cells and immunosuppressive cells within the tumor microenvironment (TME) employ multi-dimensional mechanisms to dysregulate MHC expression and function-including epigenetic silencing, autophagic degradation, and interference with transcription factors such as NLRC5 (for MHC-I) and CIITA (for MHC-II). These mechanisms enable immune escape and limit the efficacy of cancer immunotherapy.
Additionally, we review MHC-based therapeutic strategies-such as cytokine therapy, TCR-T cell therapy, immune checkpoint inhibitor (ICI) combination therapy, and tumor vaccine therapies-that have been developed to restore MHC function and overcome immune escape. A deeper understanding of the regulatory networks governing MHC molecules in tumor immunity will provide critical insights for the development of precise and effective immunotherapeutic strategies, ultimately improving clinical outcomes for cancer patients.
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