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:Intra-lesion injection of activated Natural Killer (NK) cells in recurrent malignant brain tumors.
Intra-lesion injection of activated Natural Killer (NK) cells in recurrent malignant brain tumors.
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尽管对恶性脑肿瘤患者采用了多模式治疗,其中位生存期仍< 2年。近年来,NK细胞通过其直接自然细胞毒性以及通过调节树突状细胞增强肿瘤抗原呈递和调控T细胞介导的抗肿瘤反应,提供了癌症免疫监视。
然而,这种治疗方式在脑肿瘤中的成功尚不明确。主要原因有:脑肿瘤微环境、NK细胞制剂和给药方式,以及供者选择。我们之前的研究表明,颅内注射活化的单倍体相合NK细胞可在动物模型中根除胶质母细胞瘤瘤块,且无任何肿瘤复发证据。
因此,在本研究中,我们评估了在6例对化疗/放疗耐药的复发性多形性胶质母细胞瘤(GBM)和恶性脑肿瘤患者中,手术腔内或脑脊液(CSF)内注射体外活化的单倍体相合NK细胞的安全性。
我们的结果表明,活化的单倍体相合NK细胞表达活化性和抑制性标志物,并能杀伤肿瘤细胞。然而,它们对患者来源的GBM(PD-GBM)的细胞毒性潜力高于其细胞系。
此外,其输注使总体疾病控制率提高了约33.3%,平均生存期为400天。此外,我们表明,在恶性脑肿瘤中局部给予活化的单倍体相合NK细胞是安全的、可行的、可耐受更高剂量且具有成本效益的。
Despite multi-modal therapies for patients with malignant brain tumors, their median survival is < 2 years. Recently, NK cells have provided cancer immune surveillance through their direct natural cytotoxicity and by modulating dendritic cells to enhance the presentation of tumor antigens and regulate T-cell-mediated antitumor responses.
However, the success of this treatment modality in brain tumors is unclear. The main reasons are; the brain tumor microenvironment, the NK cell preparations and administration, and the donor selection.
Our previous study showed that intracranial injection of activated haploidentical NK cells resulted in the eradication of glioblastoma tumor mass in the animal model without any evidence of tumor recurrence.
Therefore, in the present study, we evaluated the safety of intra-surgical cavity or intra cerebrospinal fluid (CSF) Injectionofex vivoactivated haploidentical NK cells in six patients with recurrent glioblastoma multiform (GBM) and malignant brain tumors resistance to chemo/radiotherapy.
Our results indicated that activated haploidentical NK cells express activator and inhibitor markers and can kill the tumor cells.
However, their cytotoxic potential on patient-derived GBM (PD-GBM) was more than that of its cell line. Also, their infusion increased the overall disease control rate by about 33. 3%, with a mean survival of 400 days.
Moreover, we showed that local administration of the activated haploidentical NK cells in malignant brain tumors is safe, feasible, tolerated at higher doses, and cost-effective.
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