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
外周 NK 细胞被确定为接受一线免疫治疗联合化疗的广泛期小细胞肺癌患者疗效的预测指标
英文原题：Peripheral NK cells identified as the predictor of response in extensive-stage small cell lung cancer patients treated with first-line immunotherapy plus chemotherapy.
查看英文原题
Peripheral NK cells identified as the predictor of response in extensive-stage small cell lung cancer patients treated with first-line immunotherapy plus chemotherapy.
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研究概要
在广泛期小细胞肺癌（ES-SCLC）患者中，外周 NK 细胞的百分比及其变化可预测对联合免疫治疗与化疗的应答。
中文摘要
目的
免疫治疗可改善广泛期小细胞肺癌（ES-SCLC）结局，但寻找可预测治疗成功的生物标志物至关重要。NK 细胞可能是多种癌症的指标，但其在 ES-SCLC 预后中的确切作用仍不明确。
方法
本回顾性研究纳入 33 例接受一线免疫化疗的 ES-SCLC 患者。采用流式细胞术分析外周血 NK 细胞比例及其纵向变化，并以风险比（HR）计算无进展生存期（PFS）和总生存期（OS）并进行统计比较。
结果
基线 NK 细胞水平正常组的中位 PFS 优于低水平组（7.0 对 4.6 个月；HR=0.17；95% CI 0.07–0.41；P<0.0001），但与 OS 无相关性（14.9 对 10.3 个月；HR=0.55；95% CI 0.23–1.31；P=0.171）。此外，在临床应答组中，95.0% 患者免疫化疗后 NK 细胞比例升高（P=0.0047），且该组中位 PFS（6.3 对 2.1 个月；HR=0.23；95% CI 0.05–0.98；P<0.0001）和 OS（14.9 对 5.9 个月；HR=0.20；95% CI 0.04–1.02；P<0.0001）更长。直至疾病进展的 NK 细胞比例变化也呈现类似趋势，并改善 PFS（6.5 对 4.3 个月；HR=0.41；95% CI 0.12–0.92；P=0.0049）和 OS（17.4 对 9.7 个月；HR=0.42；95% CI 0.17–1.02；P<0.0001）。
结论
ES-SCLC 患者外周血 NK 细胞比例及其变化可预测免疫化疗应答。
展开英文摘要原文
PURPOSE
Although immunotherapy improves outcomes in extensive-stage small-cell lung cancer (ES-SCLC), the search for biomarkers predicting treatment success is crucial. Natural killer (NK) cells are potential indicators in various cancers, however, their precise role in ES-SCLC prognosis remains unclear.
METHODS
In this retrospective study, 33 patients with ES-SCLC treated with first-line immuno-chemotherapy were enrolled. The peripheral NK cell percentage and its longitudinal dynamics were analyzed using flow cytometry. Progression-free survival (PFS) and overall survival (OS) were calculated as hazard ratio (HR) and compared statistically.
RESULTS
The median PFS was better in the group with normal baseline NK cell levels than the low group (7.0 vs. 4.6 months; HR = 0.17; 95% CI 0.07-0.41; P < 0.0001), but there was no association with OS (14.9 vs. 10.3 months; HR = 0.55; 95% CI 0.23-1.31; P = 0.171). Furthermore, the NK cell% for 95.0% of patients increased after immunochemotherapy in the clinical response group (P = 0.0047), which led to a better median PFS (6.3 vs. 2.1 months; HR = 0.23; 95% CI 0.05-0.98; P < 0.0001) and OS (14.9 vs. 5.9 months; HR = 0.20; 95% CI 0.04-1.02; P < 0.0001). Similar trends were observed with NK cell% changes up to disease progression, improving PFS (6.5 vs. 4.3; HR = 0.41; 95% CI 0.12-0.92; P = 0.0049) and OS (17.4 vs. 9.7; HR = 0.42; 95% CI 0.17-1.02; P < 0.0001).
CONCLUSION
In patients with ES-SCLC, the percentage and changes in peripheral NK cells can predict the response to combined immunotherapy and chemotherapy.
论文信息
- 作者
- Cui Y、Chen Y、Zhao P、Li S、Cheng Y、Ren X
- 第一作者单位
- Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin, 300060, China.China
- 通讯作者单位
- Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin, 300060, China. renxiubao@tjmuch.com.China
- 期刊
- Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico2024 Oct
- 原文标识
- PubMed 38662170 · DOI 10.1007/s12094-024-03479-4