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:Alpha-fetoprotein predicts the treatment efficacy of immune checkpoint inhibitors for gastric cancer patients.
Alpha-fetoprotein predicts the treatment efficacy of immune checkpoint inhibitors for gastric cancer patients.
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基线 AFP 水平可能预测 AGC 患者免疫检查点抑制剂治疗的疗效。
免疫检查点抑制剂(ICIs)常与化疗联合使用,以改善胃癌患者的治疗结局。由于AFP可通过抑制自然杀伤(NK)细胞并负向调节树突状细胞功能来影响免疫,我们评估了基线血清甲胎蛋白(AFP)水平对晚期胃癌(AGC)患者ICIs疗效的影响。
对158例接受ICI治疗的AGC患者进行了回顾性分析。根据AFP阈值20 ng/ml将患者分为高、低两组。采用ORR、DCR、PFS和OS评估ICI治疗的疗效。
基线AFP水平较高与ICIs疗效降低相关,高AFP水平组的DCR为50.0%,而低AFP水平组为87.7%(P < 0.001)。进一步使用Kaplan-Meier生存分析表明,高AFP水平与接受ICIs治疗的AGC患者较短的无进展生存期(PFS)(P < 0.001)和总生存期(OS)(P = 0.001)相关。倾向性评分匹配后,log rank检验显示,高AFP组的中位PFS(P = 0.011)和中位OS(P = 0.036)较低AFP组缩短。在ICI联合化疗患者的亚组分析中,高AFP水平也显示与较短的PFS和OS相关。
Immune checkpoint inhibitors (ICIs) are commonly used in conjunction with chemotherapy to improve treatment outcomes for patients with gastric cancer. Since AFP could influence immunity by both inhibiting natural killer (NK) cells and regulating negatively the function of dendritic cells, we evaluated the influence of baseline serum alpha-fetoprotein (AFP) levels on the curative effect of ICIs in advanced gastric cancer (AGC) patients.
A retrospective analysis was conducted on 158 AGC patients who underwent ICI treatment. The patients were divided into high and low groups based on the AFP threshold of 20 ng/ml. The efficacy of ICI treatment was assessed using objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), and overall survival (OS).
The higher levels of baseline AFP were found to be associated with a decrease in the effectiveness of ICIs, as evidenced by a DCR of 50.0% in the group with high AFP levels compared to 87.7% in the group with low AFP levels (P < 0.001). Further analysis using Kaplan-Meier survival techniques indicated that a high AFP level was linked to shorter progression-free survival (PFS) (P < 0.001) and overall survival (OS) (P = 0.001) in AGC individuals receiving ICIs. After propensity score matching, a log rank test revealed that the high AFP group had a decrease in median PFS (P = 0.011) and median OS (P = 0.036) compared to the low AFP group. The high AFP levels also showed its association with shorter PFS and OS in the subgroup analysis of ICI plus chemotherapy patients.
Baseline AFP levels may predict immune checkpoint inhibitor treatment efficacy in AGC patients.
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