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:Immunological Biomarkers in Glioblastoma: Targeting T and NK Cells for Enhanced Diagnosis and Prognosis.
Immunological Biomarkers in Glioblastoma: Targeting T and NK Cells for Enhanced Diagnosis and Prognosis.
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胶质母细胞瘤(GBM)是一种侵袭性脑肿瘤,即使采用手术、化疗和放疗等多种治疗,预后仍然较差。近期免疫疗法拓展了利用免疫系统清除GBM的前景,但由于肿瘤具有多方面免疫抑制性微环境及血脑屏障结构,此类方法的临床疗效有限。GBM中的免疫抑制机制显著影响免疫细胞功能,尤其是T细胞和自然杀伤(NK)细胞,因此需要新型治疗策略来克服这些机制。本综述探讨T细胞(尤其是细胞毒性CD4+和辅助性CD8+ T细胞)以及NK细胞应对GBM的主要功能。我们进一步讨论导致其功能障碍的机制,重点关注T细胞耗竭、受体表达改变及GBM微环境中的代谢重编程,并探讨建立诊断和预后生物标志物的依据。此外,我们介绍免疫治疗的最新进展,包括免疫检查点抑制剂(ICI)、miRNA治疗、溶瘤病毒及嵌合抗原受体(CAR)T/NK细胞疗法,为增强GBM治疗和生物标志物指导的精准医疗提供新机会。
Glioblastoma (GBM) is an aggressive brain tumor with a poor prognosis, even with many therapeutic interventions, including surgery, chemotherapy, and radiotherapy. Recent immunotherapies have broaden horizons to the utilization of the immune system to eradicate GBM.
However, the clinical efficacy of such approaches is limited, owing to the tumor's multifaceted immunosuppressive microenvironment and the blood-brain barrier (BBB) structure. The dysfunction of immune cells, especially T cells and natural killer (NK) cells, is significantly influenced by the immunosuppressive mechanisms in GBM. Novel therapeutic strategies are needed to overcome these mechanisms. In the current review, we explore the main functions of T cells, especially cytotoxic CD4 + and helper CD8 + T cells, alongside NK cells, in response to GBM.
We further discuss the mechanisms contributing to their dysfunction, focusing on T cell exhaustion, altered receptor expression, and metabolic reprogramming within the GBM microenvironment to establish diagnostic and prognostic biomarkers.
Moreover, we highlight recent advances in immunotherapeutic approaches, including immune checkpoint inhibitors (ICI), miRNA therapy, oncolytic viruses, and Chimeric Antigen Receptor (CAR) T/NK cell therapy to provide new opportunities for enhancing GBM treatment and biomarker-guided precision medicine.
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