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:Gross Total Resection Promotes Subsequent Recovery and Further Enhancement of Impaired Natural Killer Cell Activity in Glioblastoma Patients.
Gross Total Resection Promotes Subsequent Recovery and Further Enhancement of Impaired Natural Killer Cell Activity in Glioblastoma Patients.
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胶质母细胞瘤是最常见的原发性恶性脑肿瘤,尽管接受积极标准治疗,中位生存期仍较短。自然杀伤(NK)细胞功能障碍与肿瘤复发和转移密切相关,但其在胶质母细胞瘤中的情况尚不明确。NK活性(NKA)代表NK细胞分泌的干扰素-γ(IFN-γ),可调节免疫并抑制癌症进展。
本研究旨在分析胶质母细胞瘤患者的NKA,以更清楚了解免疫监视情况。2020至2021年间共纳入20例患者和6名健康对照。分别于术前及术后第3天和第30天采集外周血,使用NK VUE试剂盒测量NKA。NKA在术后第3天降低,但随后恢复,并于术后第30天显著升高,达到基线近5倍(p=0.004)。
此外,CD56bright CD16− NK细胞比例在术后第3天显著降低(p=0.022),并于术后第30天进一步恢复。按手术切除范围进行亚组分析显示,受损NKA恢复归因于全切除(GTR),而非次全切除(STR)。
总之,胶质母细胞瘤患者NKA显著受损;GTR在改善受抑NKA和CD56bright CD16− NK细胞亚群方面显示更大获益,可能与后续患者预后相关。
因此,只要可行,应以胶质母细胞瘤GTR为目标,因为这似乎可增强NKA细胞免疫。
Glioblastoma is the most common primary malignant brain tumor, and median survival is relatively short despite aggressive standard treatment. Natural killer (NK) cell dysfunction is strongly associated with tumor recurrence and metastasis but is unclear in glioblastoma. NK activity (NKA) represents NK cell-secreted interferon- (IFN- ), which modulates immunity and inhibits cancer progression.
This study aimed to analyze NKA in glioblastoma patients to obtain a clearer overview of immunity surveillance. From 2020 to 2021, a total of 20 patients and six healthy controls were recruited. Peripheral blood samples were collected preoperatively and on postoperative days (POD) 3 and 30. Then, NKA was measured using the NK VUE kit. Although NKA decreased on POD3, it recovered and further significantly enhanced on POD30, with a nearly five-fold increase compared to baseline ( p = 0. 004).
Furthermore, the percentage of CD56 bright CD16 - NK cells decreased significantly on POD3 ( p = 0. 022) and further recovered on PO30. Subgroup analysis of extent surgical resection further revealed that the recovery of impaired NKA was attributable to gross total resection (GTR) rather than subtotal resection (STR).
In conclusion, NKA is significantly impaired in glioblastoma, and GTR has demonstrated superior benefit in improving the suppressed NKA and increased CD56 bright CD16 - NK subset in glioblastoma patients, which may be associated with subsequent patients' prognosis.
Therefore, the goal of performing GTR for glioblastoma should be achieved when possible since it appears to increase NKA cell immunity.
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