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.
肿瘤细胞治疗研究
英文原题:Innate immune networks in glioblastoma: Cellular plasticity, immune crosstalk, and therapeutic implications.
Innate immune networks in glioblastoma: Cellular plasticity, immune crosstalk, and therapeutic implications.
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胶质母细胞瘤(GB),根据2021年世界卫生组织分类,在此主要定义为成人型异柠檬酸脱氢酶野生型高级别胶质瘤,是一种侵袭性原发性脑肿瘤,其特征为局部和全身性免疫抑制、治疗耐药以及不良的临床结局。尽管大量关注集中于GB中的适应性免疫应答,先天免疫细胞在肿瘤微环境中发挥核心调控作用。它们可能影响肿瘤进展、免疫逃逸和治疗反应。各先天免疫细胞群体的证据强度差异很大,从特征较为明确的髓系细胞群,如肿瘤相关巨噬细胞、树突状细胞、髓源性抑制细胞和中性粒细胞,到研究较少的粒细胞和淋巴样亚群,包括NK 细胞、先天淋巴样细胞、嗜酸性粒细胞、肥大细胞和嗜碱性粒细胞。在本综述中,我们讨论这些细胞在肿瘤监视和促进中的情境依赖性作用、它们与GB干样细胞的相互作用、它们对免疫抑制和治疗耐药的贡献,以及它们作为预后生物标志物或治疗靶点的潜在相关性。通过整合临床观察与实验证据,我们重点介绍当前在GB中重编程先天免疫的策略,并指出在基于先天免疫的方法能够更有效地转化为临床实践之前必须解决的关键局限性。
Glioblastoma (GB), defined here primarily as adult-type Isocitrate dehydrogenase-wildtype high-grade glioma, according to the 2021 World Health Organization classification, is an aggressive primary brain tumor characterized by local and systemic immunosuppression, therapeutic resistance, and poor clinical outcomes. Although considerable attention has focused on adaptive immune responses in GB, innate immune cells centrally regulate the tumor microenvironment. They may influence tumor progression, immune evasion, and treatment response. The strength of evidence varies substantially across innate immune populations, ranging from well-characterized myeloid compartments, such as tumor-associated macrophages, dendritic cells, myeloid-derived suppressor cells, and neutrophils, to less explored granulocytic and lymphoid subsets, including natural killer cells, innate lymphoid cells, eosinophils, mast cells, and basophils.
In this review, we discuss the context-dependent roles of these cells in tumor surveillance and promotion, their interactions with GB stem-like cells, their contributions to immunosuppression and therapeutic resistance, and their potential relevance as prognostic biomarkers or therapeutic targets.
By integrating clinical observations with experimental evidence, we highlight current strategies to reprogram innate immunity in GB and identify key limitations that must be addressed before innate immune-based approaches can be translated more effectively into clinical practice.
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