不适合移植的大 B 细胞淋巴瘤二线使用 axicabtagene ciloleucel:ALYCANTE 最终分析
Second-line axicabtagene ciloleucel in large B-cell lymphoma ineligible for transplantation: ALYCANTE final analysis.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Adverse Effects of Low Serum HDL-C Levels on Prognosis and Tumor Immune Microenvironment in Patients With Newly Diagnosed Chronic Lymphocytic Leukemia.
Adverse Effects of Low Serum HDL-C Levels on Prognosis and Tumor Immune Microenvironment in Patients With Newly Diagnosed Chronic Lymphocytic Leukemia.
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脂质代谢紊乱促进包括慢性淋巴细胞白血病(CLL)在内的血液系统恶性肿瘤的发生和进展。本研究旨在探讨CLL患者血清脂质水平与预后之间的关联。
我们回顾性分析了142例新诊断CLL(ND-CLL)患者的数据。我们的生存分析显示,低水平的高密度脂蛋白胆固醇/载脂蛋白-A1(HDL-C/ApoA1)与ND-CLL患者较差的总生存期(OS)和无进展生存期相关。多因素分析确定HDL-C是OS的独立危险因素。与仅基于经典预后因素的预测相比,结合HDL-C水平和经典预后因素的列线图提高了预测5年OS的准确性。低水平HDL-C对CLL患者预后的不良影响通过外部验证得到进一步证实,其中通过在包含448例CLL患者的队列中评估胆固醇外流来模拟HDL-C的功能。
此外,对194例外周血淋巴细胞亚群的流式细胞术分析表明,HDL-C/ApoA1水平与自然杀伤(NK)细胞呈显著正相关。随后的体外细胞实验证实了HDL增强NK细胞细胞毒性的能力,表现为CD107a和肿瘤坏死因子-α表达水平升高。
总之,低血清HDL-C水平与ND-CLL患者不良预后相关,可能归因于NK细胞细胞毒性受损,这为HDL-C的预后作用提供了见解,并为ND-CLL患者提出了一个新的潜在治疗靶点。
Disorders of lipid metabolism contribute to the occurrence and progression of hematological malignancies, including chronic lymp hocytic leukemia (CLL). The objective of this study was to investigate the association between serum lipid levels and prognosis in patients with CLL.
We retrospectively analyzed data from 142 patients with newly diagnosed CLL (ND-CLL).
Our survival analysis showed that low levels of high-density lipoprotein cholesterol/Apolipoprotein-A1 (HDL-C/ApoA1) were associated with poor overall survival (OS) and progression-free survival in patients with ND-CLL. Multivariate analysis identified HDL-C as an independent hazard element for OS.
A nomogram combining HDL-C levels and classical prognostic factors increased the accuracy of predicting 5-year OS compared to prediction based solely on classical prognostic factors. The adverse effect of low levels of HDL-C on prognosis in CLL patients was further validated through external validation, wherein the functionality of HDL-C was simulated by assessing cholesterol efflux in a cohort comprising 448 CLL patients.
Moreover, flow cytometry analysis of 194 peripheral blood lymphocyte subpopulations demonstrated that the levels of HDL-C/ApoA1 was significantly positively correlated with natnatural killer (NK) cells. Subsequent in vitro cell experiments confirmed the ability of HDL to augment NK cell cytotoxicity, as evidenced by elevated expression levels of CD107a and tumor necrosis factor-α.
In conclusion, low serum HDL-C levels are related to a poor prognosis in patients with ND-CLL, potentially due to impaired NK cell cytotoxicity, providing insight into the prognostic role of HDL-C and proposing a new potential therapeutic target in patients with ND-CLL.
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