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:Monitoring Blood Immune Cells in Patients with Advanced Small Cell Lung Cancer Undergoing a Combined Immune Checkpoint Inhibitor/Chemotherapy.
Monitoring Blood Immune Cells in Patients with Advanced Small Cell Lung Cancer Undergoing a Combined Immune Checkpoint Inhibitor/Chemotherapy.
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本项探索性前瞻性观察研究纳入40例接受化疗联合免疫检查点抑制剂治疗的小细胞肺癌(SCLC)患者,通过多色流式细胞术检测基线及第3个治疗周期时的血液免疫细胞。研究测定中性粒细胞及T、B、NK细胞数量,以及HLA-DR低表达单核细胞、6-磺基唾液酸乳糖N-乙酰基(slan)阳性非经典单核细胞和循环树突状细胞(DC)亚型的频率。以总生存期(OS)为主要终点,通过患者生存分析评估上述参数的预后价值。
此外,将SCLC患者的血细胞参数与非小细胞肺癌(NSCLC)患者进行比较。患者整体OS中位数为10.4±1.1个月。疾病进展患者(占15%)基线中性粒细胞/淋巴细胞比值(NLR)较高、HLA-DR低表达单核细胞较多,NK细胞和DC数量较低。OS不良的风险因素包括脑/肝转移、基线NLR≥6.1、HLA-DR低表达单核细胞占单核细胞≥21%、slan⁺非经典单核细胞占比<0.12%和/或CD1c⁺髓系DC占白细胞<0.05%。淋巴细胞亚群与OS无相关性。与NSCLC相比,SCLC患者脑/肝转移频率更高、NLR更高、DC频率最低且NK细胞数量更少。脑/肝转移对SCLC患者生存有显著影响。基线时,45%的SCLC患者存在3至5项风险因素,而NSCLC患者中这一比例仅为24%。在所有肺癌组织学类型中,基线NLR高、HLA-DR低表达单核细胞频率高以及slan⁺非经典单核细胞水平低均与生存不良相关。
因此,血液免疫细胞特征可能有助于更准确地预测SCLC患者结局,并揭示该肿瘤类型的病理生理学特点。
In this exploratory prospective observational study on 40 small cell lung cancer (SCLC) patients treated with a combination of chemotherapy and immune checkpoint inhibitors, blood immune cells were characterized by multi-color flow cytometry at the baseline and at the third therapy cycle.
The numbers of neutrophils and of T-, B-, and NK cells, as well as the frequency of HLA-DR low monocytes, 6-SulfoLacNAc (slan)+ non-classical monocytes and circulating dendritic cell (DC) subtypes were determined. The prognostic value of the parameters was evaluated by the patient's survival analysis with overall survival (OS) as the primary endpoint.
In addition, blood cell parameters from SCLC patients were compared to those from non-SCLC (NSCLC). The global median OS of patients was 10. 4 1. 1 months. Disease progression (15% of patients) correlated with a higher baseline neutrophil/lymphocyte ratio (NLR), more HLA-DR low monocytes, and lower NK cell and DC numbers. The risk factors for poor OS were the presence of brain/liver metastases, a baseline NLR 6. 1, HLA-DR low monocytes 21% of monocytes, slan+ non-classical monocytes < 0. 12%, and/or CD1c+ myeloid DC < 0. 05% of leukocytes.
Lymphocytic subpopulations did not correlate with OS. When comparing biomarkers in SCLC versus NSCLC, SCLC had a higher frequency of brain/liver metastases, a higher NLR, the lowest DC frequencies, and lower NK cell numbers. Brain/liver metastases had a substantial impact on the survival of SCLC patients.
At the baseline, 45% of SCLC patients, but only 24% of NSCLC patients, had between three and five risk factors. A high basal NLR, a high frequency of HLA-DR low monocytes, and low levels of slan+ non-classical monocytes were associated with poor survival in all lung cancer histotypes.
Thus, the blood immune cell signature might contribute to a better prediction of SCLC patient outcomes and may uncover the pathophysiological peculiarities of this tumor entity.
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