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:Recent advances in immunotherapy for gliomas: overcoming barriers and advancing precision strategies.
Recent advances in immunotherapy for gliomas: overcoming barriers and advancing precision strategies.
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胶质瘤,尤其是胶质母细胞瘤(GBM),仍是最致命的原发性脑肿瘤之一,治疗结局受显著瘤内异质性、深度免疫抑制性肿瘤微环境(TME)和限制性血脑屏障(BBB)制约。免疫检查点抑制剂、嵌合抗原受体(CAR)T和NK细胞以及溶瘤病毒疗法等免疫疗法虽已改变其他恶性肿瘤治疗范式,但在胶质瘤中的疗效有限,受肿瘤突变负荷低、抗原可塑性、代谢抑制和治疗相关免疫抑制等因素影响。多抗原靶向、代谢重编程和创新递送策略等近期进展提高了临床前疗效;ADAMTSL4、ACSS3和影像组学衍生免疫特征等新兴生物标志物的整合,则为精准患者分层提供了机会。实时分子监测、空间免疫分析和合理设计联合方案等方面的进展正在汇聚,有望重新校准胶质瘤免疫环境,推动具有临床意义且持久的免疫治疗应答。
Gliomas, and particularly glioblastoma (GBM), remain among the most lethal primary brain tumors, with outcomes constrained by extensive intra tumor heterogeneity, a profoundly immunosuppressive tumor microenvironment (TME), and the restrictive nature of the blood-brain barrier (BBB). Although immunotherapies, including immune checkpoint inhibitors, chimeric antigen receptor (CAR) T and NK cells, and oncolytic virotherapy, have redefined treatment paradigms in other malignancies, their efficacy in gliomas has been modest, limited by low tumor mutational burden, antigenic plasticity, metabolic suppression, and therapy-associated immunosuppression.
Recent advances in multi-antigen targeting, metabolic reprogramming, and innovative delivery strategies have enhanced preclinical efficacy, while the integration of emerging biomarkers such as ADAMTSL4, ACSS3, and radiomics-derived immune signatures offers opportunities for precision patient stratification.
Converging developments in real-time molecular monitoring, spatial immunoprofiling, and rationally designed combination regimens hold the potential to recalibrate the glioma immune landscape, paving the way toward clinically impactful and durable immunotherapeutic responses.
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