RNF43 p.G659fs 通过 PI3K/AKT/mTOR 信号通路和 HLA-E 上调导致 MSI-high 结直肠癌中 NK 细胞功能障碍
RNF43 p.G659fs leads to natural killer cell dysfunction in MSI-high colorectal cancer through PI3K/AKT/mTOR signaling and HLA-E up-regulation.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Cellular characteristics of the immune microenvironment of colorectal cancer and progress in immunotherapy research.
Cellular characteristics of the immune microenvironment of colorectal cancer and progress in immunotherapy research.
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结直肠癌(CRC)仍然是全球癌症相关死亡的主要原因,其进展和治疗结局在很大程度上受到肿瘤免疫微环境(TME)复杂性和异质性的影响。本综述批判性地探讨了驱动CRC免疫逃逸的细胞和分子机制,重点阐述了免疫细胞群体——包括肿瘤相关巨噬细胞、中性粒细胞、树突状细胞、T细胞、B细胞和NK 细胞——的双重作用,以及细胞外基质和细胞外囊泡等非细胞成分。
一个关键目标是评估免疫治疗方法的近期进展,包括免疫检查点抑制剂、肿瘤疫苗、过继性细胞转移和新型联合方案,同时探讨其治疗前景和固有局限性,尤其是在对标准免疫治疗表现出原发性抵抗的微卫星稳定(MSS)肿瘤中。进一步的分析整合了关于TME内代谢重编程、表观遗传改变以及工程化细胞疗法进展的观点,从而为克服免疫抑制机制提供了一个全面的框架。讨论与结论:特别关注靶向TME内免疫-代谢相互作用和空间动态的转化价值。最终,这项工作综合了当前知识,并概述了推进个性化、多靶点免疫治疗的前瞻性策略,有望重塑CRC管理的临床范式。
Colorectal cancer (CRC) continues to represent a major cause of cancer-related mortality worldwide, with its progression and therapeutic outcomes strongly shaped by the complexity and heterogeneity of the tumor immune microenvironment (TME). This review critically examines the cellular and molecular mechanisms driving immune evasion in CRC, emphasizing the dual roles of immune cell populations-including tumor-associated macrophages, neutrophils, dendritic cells, T cells, B cells, and natural killer cells-as well as non-cellular elements such as the extracellular matrix and extracellular vesicles.
A key objective is to evaluate recent developments in immunotherapeutic approaches, including immune checkpoint inhibitors, tumor vaccines, adoptive cell transfer, and novel combinatorial regimens, while addressing their therapeutic promise and inherent limitations, especially in microsatellite-stable (MSS) tumors that exhibit primary resistance to standard immunotherapies. Further analysis integrates perspectives on metabolic reprogramming within the TME, epigenetic alterations, and advances in engineered cellular therapies, thereby providing a comprehensive framework for overcoming immunosuppressive mechanisms. DISCUSSION AND CONCLUSION: Special consideration is directed toward the translational value of targeting immune-metabolic interactions and spatial dynamics within the TME. Ultimately, this work synthesizes current knowledge and outlines forward-looking strategies to advance personalized, multi-target immunotherapy, with the potential to reshape clinical paradigms in CRC management.
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