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:Reduced Peripheral Blood Natural Killer Cell Proportion Predicts Poor Overall Survival in Advanced Gastric Cancer Patients Treated With Apatinib.
Reduced Peripheral Blood Natural Killer Cell Proportion Predicts Poor Overall Survival in Advanced Gastric Cancer Patients Treated With Apatinib.
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阿帕替尼联合 S-1 作为 AGC 患者二线治疗方案,表现出良好的耐受性和有前景的临床活性。重要的是,我们确定外周血 NK 细胞比例是治疗反应的潜在预测因子,其中 NK 细胞比例低与较差的结果相关。
血管生成抑制是肿瘤学中的关键治疗策略,阿帕替尼在晚期胃癌(AGC)治疗中显示出显著疗效。目前,尚无生物标志物能够可靠预测哪些AGC患者将从阿帕替尼中获益最多。本研究的目的是评估阿帕替尼联合替吉奥胶囊(S-1)作为AGC二线治疗的效果,并探讨与结局相关的预后生物标志物。
所有60例患者均接受阿帕替尼(250或500 mg,每日一次)联合S-1(40 mg/m 2,第1天至第14天每日两次)治疗。治疗以28天为一个周期,每疗程包含两个这样的周期。采用多参数流式细胞术分析AGC患者外周血单个核细胞样本中T细胞和自然杀伤(NK)细胞的亚群分布及免疫表型。
在所有60例可评估患者中,未观察到完全缓解。33.3%(20/60)的患者出现部分缓解(95% CI:21.1-45.6%),38.3%(23/60)的患者出现疾病稳定(95% CI:25.7-51.0%),而28.3%的患者出现疾病进展(95% CI:16.6-40.1%)。值得注意的是,NK细胞比例大于17%的患者比比例较低的患者具有更长的PFS和OS。
Angiogenesis inhibition represents a key therapeutic strategy in oncology, with apatinib showing significant efficacy for advanced gastric cancer (AGC) therapy. Currently, no biomarkers can reliably predict which AGC patients will benefit most from apatinib. The purpose of this study was to evaluate apatinib plus tegafur gimeracil oteracil potassium capsule (S-1) as a second-line therapy in AGC and to investigate prognostic biomarkers associated with outcomes.
All 60 patients received apatinib (250 or 500 mg once daily) in combination with S-1 (40 mg/m 2 , administered twice daily from day 1 to day 14). Treatment was administered in 28-day cycles, with each course encompassing two such cycles. Multiparameter flow cytometry was used to analyze the subset distribution and immunophenotypes of T cells and natural killer (NK) cells in peripheral blood mononuclear cell samples from AGC patients.
Among all 60 evaluable patients, no complete responses were observed. Partial responses were observed in 33.3% (20/60) of patients (95% confidence interval (CI): 21.1-45.6%), stable disease was observed in 38.3% (23/60) of patients (95% CI: 25.7-51.0%), while progressive disease occurred in 28.3% (95% CI: 16.6-40.1%). Notably, patients with NK cell proportions greater than 17% experienced longer progression-free survival (PFS) and overall survival (OS) than those with lower proportions.
Apatinib combined with S-1 exhibited favorable tolerability and promising clinical activity as a second-line option for AGC patients. Importantly, we identified peripheral blood NK cell proportion as a potential predictor of treatment response, where a low NK cell proportion correlated with poorer outcomes.
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