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:Immune surveillance in glioblastoma: Role of the NKG2D system and novel cell-based therapeutic approaches.
Immune surveillance in glioblastoma: Role of the NKG2D system and novel cell-based therapeutic approaches.
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胶质母细胞瘤,曾称为多形性胶质母细胞瘤(GBM),是成人中最常见且最具侵袭性的脑肿瘤。大脑是免疫豁免器官,血脑屏障使大脑免受免疫监视。在这篇综述中,我们讨论GBM中免疫抑制性肿瘤微环境的组成以及潜在的免疫逃逸机制。在这方面,我们重点关注NKG2D受体/配体系统的作用。NKG2D配体经常在GBM肿瘤细胞上表达,并可激活表达NKG2D的杀伤细胞,包括NK细胞和γδ T细胞。然而,可溶性NKG2D配体有助于肿瘤逃避免疫攻击。我们还讨论了当前旨在改善GBM患者生存的免疫治疗策略。此类方法包括调节NKG2D受体/配体系统、应用检查点抑制剂、过继转移体外扩增和/或修饰的免疫细胞,或应用抗体及抗体构建体在体内靶向细胞毒性效应细胞。鉴于所追求的策略众多,未来GBM患者总生存期有望得到改善。
Glioblastoma, formerly known as glioblastoma multiforme (GBM), is the most frequent and most aggressive brain tumour in adults. The brain is an immunopriviledged organ, and the blood-brain barrier shields the brain from immune surveillance. In this review, we discuss the composition of the immunosuppressive tumour micromilieu and potential immune escape mechanisms in GBM.
In this respect, we focus on the role of the NKG2D receptor/ligand system. NKG2D ligands are frequently expressed on GBM tumour cells and can activate NKG2D-expressing killer cells including NK cells and γδ T cells. Soluble NKG2D ligands, however, contribute to tumour escape from immunological attack.
We also discuss the current immunotherapeutic strategies to improve the survival of GBM patients. Such approaches include the modulation of the NKG2D receptor/ligand system, the application of checkpoint inhibitors, the adoptive transfer of ex vivo expanded and/or modified immune cells or the application of antibodies and antibody constructs to target cytotoxic effector cells in vivo. In view of the multitude of pursued strategies, there is hope for improved overall survival of GBM patients in the future.
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