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:Immunocytes in the tumor microenvironment: recent updates and interconnections.
Immunocytes in the tumor microenvironment: recent updates and interconnections.
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肿瘤微环境(TME)是一个复杂且动态的生态系统,其中肿瘤细胞与多种免疫及基质细胞相互作用。本综述概述TME组成变化,强调其由早期促炎、免疫促进状态转向后期免疫抑制状态,后者以代谢重编程和缺氧为特征。文中重点介绍关键免疫细胞的双重作用,包括T淋巴细胞、NK 细胞、巨噬细胞、树突状细胞和髓源性抑制细胞;其可依据表型极化和局部代谢条件抑制或支持肿瘤进展。文章还阐明免疫细胞可塑性的机制,如巨噬细胞M1/M2转换及效应T细胞与调节性T细胞的平衡,并强调其对肿瘤生长和转移的影响。此外,免疫检查点抑制剂、嵌合抗原受体(CAR)T/NK细胞疗法及靶向代谢通路等新兴策略,有望重新激活抗肿瘤免疫。通过整合近期分子机制认识和临床进展,本文强调阐明免疫细胞与TME相互作用对于开发更有效癌症免疫疗法的重要性。
The tumor microenvironment (TME) is a complex, dynamic ecosystem where tumor cells interact with diverse immune and stromal cell types. This review provides an overview of the TME's evolving composition, emphasizing its transition from an early pro-inflammatory, immune-promoting state to a later immunosuppressive milieu characterized by metabolic reprogramming and hypoxia.
It highlights the dual roles of key immunocytes-including T lymphocytes, natural killer cells, macrophages, dendritic cells, and myeloid-derived suppressor cells-which can either inhibit or support tumor progression based on their phenotypic polarization and local metabolic conditions. The article further elucidates mechanisms of immune cell plasticity, such as the M1/M2 macrophage switch and the balance between effector T cells and regulatory T cells, underscoring their impact on tumor growth and metastasis.
Additionally, emerging therapeutic strategies, including checkpoint inhibitors and chimeric antigen receptor (CAR) T and NK cell therapies, as well as approaches targeting metabolic pathways, are discussed as promising avenues to reinvigorate antitumor immunity. By integrating recent molecular insights and clinical advancements, the review underscores the importance of deciphering the interplay between immunocytes and the TME to develop more effective cancer immunotherapies.
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