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:Decoding the immune landscape in Ewing sarcoma pathogenesis: The role of tumor infiltrating immune cells and immune milieu.
Decoding the immune landscape in Ewing sarcoma pathogenesis: The role of tumor infiltrating immune cells and immune milieu.
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Ewing肉瘤(EwS)是第二常见的儿童骨恶性肿瘤,以侵袭性强和预后不良为特征。EwS的肿瘤微环境(TME)由免疫抑制成分塑造,包括髓源性抑制细胞、肿瘤相关巨噬细胞以及免疫检查点分子如PD-1/PD-L1和HLA-G。这些元素通过调节肿瘤浸润免疫细胞(如调节性T细胞(Tregs)、CD8+ T细胞和NK 细胞)的功能,损害抗肿瘤免疫应答。趋化因子(包括CXCL9和CXCL12)和细胞因子(如转化生长因子-β和白细胞介素-10)进一步促进免疫抑制并推动转移播散。免疫治疗的最新进展凸显了调节免疫细胞和信号通路以增强抗肿瘤免疫的治疗潜力。本综述对EwS TME内复杂的免疫景观进行了全面分析,重点关注关键免疫成分的机制作用及其作为治疗靶点的潜力。理解这些相互作用可为创新治疗策略铺平道路,以改善EwS患者的临床结局。
Ewing sarcoma (EwS) is the second most prevalent pediatric bone malignancy, characterized by its aggressive behavior and unfavorable prognosis. The tumor microenvironment (TME) of EwS is shaped by immunosuppressive components, including myeloid-derived suppressor cells, tumor-associated macrophages, and immune checkpoint molecules such as PD-1/PD-L1 and HLA-G. These elements impair anti-tumor immune responses by modulating the function of tumor-infiltrating immune cells, such as regulatory T cells (Tregs), CD8 + T cells, and natural killer cells.
Chemokines, including CXCL9 and CXCL12, and cytokines, such as transforming growth factor-beta and interleukin-10, further contribute to immune suppression and promote metastatic dissemination. Recent advances in immunotherapy have highlighted the therapeutic potential of modulating immune cells and signaling pathways to enhance anti-tumor immunity.
This review provides a comprehensive analysis of the complex immune landscape within the EwS TME, focusing on the mechanistic roles of key immune components and their potential as therapeutic targets. Understanding these interactions could pave the way for innovative treatment strategies to improve clinical outcomes in patients with EwS.
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