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:Prognostic significance of perioperative circulating CD56(bright) NK cell and recovery of NK cell activity in patients with colorectal cancer undergoing radical surgery.
Prognostic significance of perioperative circulating CD56(bright) NK cell and recovery of NK cell activity in patients with colorectal cancer undergoing radical surgery.
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我们的研究结果提示,术后第 30 天(POD30)CD56 bright NK 细胞在百分比和比值上均显著升高,与结直肠癌患者更有利的预后相关。
前瞻性纳入45例CRC患者。术前及术后第3天(POD3)和第30天(POD30)采集静脉血样。通过测量NK细胞分泌的IFN-γ血浆水平评估NKA。
与术前基线相比,POD3时NKA显著降低,但至POD30时明显恢复。晚期疾病或术前存在至少一种高危因素患者的POD30 NKA明显较高。此外,晚期患者NKA恢复程度较高与无复发生存期(RFS)和无进展生存期(PFS)改善相关(风险比[HR]:0.2442)。术后POD30时CD56bright NK细胞比例较高及CD56bright/CD56dim NK细胞比值较高,也与更佳RFS/PFS相关(HR分别为0.2732,P=0.0433;0.2193,P=0.024)。
研究发现,术后第30天CD56bright NK细胞数量(比例和比值)显著增加,与CRC患者预后较好相关。此外,晚期患者NKA恢复率较高可能用于CRC风险分层和治疗策略开发。
We prospectively enrolled 45 patients with CRC. Venous blood samples were collected preoperatively and on postoperative day 3 (POD3) and 30 (POD30). NKA was assessed by measuring the plasma levels of NK cell-secreted IFN- .
NKA was significantly reduced on POD3 compared with baseline levels before surgery but showed significant recovery by POD30. NKA on POD30 was considerably higher in patients with advanced disease stages or one or more high-risk preoperative factors. Additionally, a higher NKA recovery in patients with advanced stage exhibited improved recurrence-free survival (RFS) and progression-free survival (PFS) (hazards ratio (HR): 0.2442). Furthermore, an increased percentage of CD56 bright NK cells and a higher CD56 bright /CD56 dim NK cell ratio postoperatively on POD30 were associated with better RFS/PFS (HR: 0.2732, P = 0.0433 and HR: 0.2193, P = 0.024, respectively).
Our findings indicate that a notable postoperative increase in CD56 bright NK cells on POD30, both in percentage and ratio, correlates with a more favorable prognosis in CRC patients. Additionally, higher recovery rates of NKA in patients with advanced stages may offer potential applications in risk stratification and the development of treatment strategies for CRC.
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