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:Dynamic monitoring of lymphocyte subsets at different disease stages can predict the prognosis of acute myeloid leukemia especially in complete remission status.
Dynamic monitoring of lymphocyte subsets at different disease stages can predict the prognosis of acute myeloid leukemia especially in complete remission status.
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急性髓系白血病(AML)缺乏有效预后标志物。尽管淋巴细胞亚群已被认为是血液系统恶性肿瘤中有价值的预测指标,但其在AML中的作用仍大多未明,尤其是不同疾病阶段的作用。
本研究分析了初诊(ND)及首次完全缓解(CR)状态下AML患者淋巴细胞亚群水平及变化,并探究不同疾病阶段淋巴细胞亚群与预后的相关性。通过流式细胞术检测145例初诊AML患者、125例CR期AML患者及47名健康对照(HC)的外周血淋巴细胞亚群;另对28例AML患者在初诊和CR期进行动态检测。
研究发现,初诊、CR期患者与健康对照的淋巴细胞亚群存在显著差异;从初诊到CR期,CD3+ T、CD4+ T、CD8+ T、效应T细胞(Teff)、B细胞和自然杀伤(NK)细胞均有明显变化。初诊组CD8+ T细胞频率低于健康对照阈值,以及调节性T细胞(Treg)频率高于健康对照阈值,均为治疗无应答的独立危险因素。采用ROC曲线评估淋巴细胞亚群的预后价值并确定截点。初诊组淋巴细胞亚群与复发或生存无显著关联。CR组CD3+ T、B和NK细胞绝对计数偏低与AML复发相关,NK细胞计数偏低是总生存期(OS)的独立预测因素。淋巴细胞亚群可作为预后生物标志物,动态监测可预测AML治疗应答、复发和生存结局。
Acute myeloid leukemia (AML) lacks effective prognostic markers. While lymphocyte subsets are recognized as valuable predictive indicators in hematologic malignancies, their role in AML remains largely unexplored, particularly during different stages of AML.
Our study analyzed the levels and changes of lymphocyte subsets in AML patients at newly diagnosed (ND) and first complete remission (CR) status, and explored the correlation between lymphocyte subsets and prognosis in different disease stages. Flow cytometry detected peripheral blood lymphocyte subsets in 145 ND AML patients, 125 CR AML patients, and 47 healthy controls (HCs). Dynamic testing was conducted on 28 AML patients at both ND and CR status.
Our study found significant differences in lymphocyte subsets between ND, CR, and HCs, with notable changes in CD3 + T, CD4 + T, CD8 + T, effector T (Teff), B, and natural killer (NK) cells between ND and CR status. Low frequencies of CD8 + T below HCs thresholds and high regulatory T cell (Treg) frequency above HCs thresholds in the ND group, were independent risk factors for non-response to treatment.
ROC curves evaluated the prognostic value of lymphocyte subsets and established cutoff values. Lymphocyte subsets in the ND group were not significantly associated with relapse or survival. Low absolute counts of CD3 + T, B, and NK cells in the CR group were linked to AML relapse, and a low NK cell count was an independent predictor of overall survival (OS). Lymphocyte subsets can act as prognostic biomarkers, and their dynamic monitoring predicts treatment response, relapse, and survival in AML.
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