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:The PD-1/PD-L1 pathway and Epstein-Barr virus.
The PD-1/PD-L1 pathway and Epstein-Barr virus.
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EBV 是一种双链 DNA 的 γ-疱疹病毒。原发性 EBV 感染可导致 20-50% 的儿童和年轻成人发生传染性单核细胞增多症(IM)。EBV 在 B 淋巴细胞中建立潜伏感染,并可感染 T 淋巴细胞和 NK 细胞,潜在引起淋巴增殖性疾病(LPD)和恶性肿瘤。尽管 PD-1/PD-L1 通路在慢性病毒感染中的作用已较为明确,但其在 EBV 感染中的具体功能仍知之甚少。越来越多的证据表明,该通路促进 EBV 免疫逃逸,然而在急性 IM 期间 PD-1 上调对 EBV 特异性 CD8+ T 细胞功能的影响尚不清楚。
此外,PD-1/PD-L1 通路在 EBV 感染期间对细胞毒性 T 细胞及免疫调节的作用仍存在争议。本综述系统分析了目前关于 PD-1/PD-L1 信号在 EBV 感染中作用的认识,聚焦于三个关键方面:(1)其在急性感染期间维持免疫稳态与可能促进病毒持续存在的双重作用;(2)其作为疾病进展和预后诊断生物标志物的新兴潜力,尤其是在急性传染性单核细胞增多症期间;(3)通路调控的治疗意义。
我们批判性评估了近期将 PD-1/PD-L1 定位于病毒学与肿瘤免疫学交叉点的研究进展,同时强调了需要进一步研究以优化 EBV 特异性免疫治疗的重要未解问题。
Epstein-Barr virus (EBV) is a gamma-herpesvirus with double-stranded DNA. Primary EBV infection leads to infectious mononucleosis (IM) in 20-50% of children and young adults. EBV establishes latent infection in B lymphocytes and can infect T lymphocytes and NK cells, potentially causing lymphoproliferative disorders (LPD) and malignancies.
While the PD-1/PD-L1 pathway's role in chronic viral infections is well-established, its specific functions in EBV infection remain poorly understood. Growing evidence suggests this pathway facilitates EBV immune evasion, yet the effect of PD-1 upregulation on Epstein-Barr virus-specific CD8 + T cell function during acute IM is unclear.
Furthermore, the role of PD-1/PD-L1 pathway in cytotoxic T cells and immune regulation during EBV infection is still controversial.
This review systematically analyzes current knowledge on PD-1/PD-L1 signaling in EBV infection, focusing on three key aspects: (1) its dual role in maintaining immune homeostasis during acute infection while potentially facilitating viral persistence, (2) its emerging potential as a diagnostic biomarker for disease progression and prognosis, particularly during acute infectious mononucleosis, and (3) the therapeutic implications of pathway modulation.
We critically evaluate recent advances that position PD-1/PD-L1 at the intersection of virology and tumor immunology, while highlighting important unanswered questions that require further investigation to optimize EBV-specific immunotherapies.
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