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卵巢癌肿瘤微环境中 Galectin-3 水平升高:提示 ROS 通过肿瘤相关中性粒细胞介导对 NK 细胞抗肿瘤反应的抑制

英文原题:Elevated Galectin-3 levels in the tumor microenvironment of ovarian cancer - implication of ROS mediated suppression of NK cell antitumor response via tumor-associated neutrophils.

查看英文原题

Elevated Galectin-3 levels in the tumor microenvironment of ovarian cancer - implication of ROS mediated suppression of NK cell antitumor response via tumor-associated neutrophils.

PubMed 2024/12/20(内容时间) Front Immunol Q1 · IF 7(JCR 2025)

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研究概要

我们的结果表明,HGSC 的肿瘤微环境中存在高水平的 Galectin-3。

中文摘要

研究从高级别浆液性癌(HGSC)患者收集转移性肿瘤微环境中的腹水、原发肿瘤部位的囊液及外周血样本。测定腹水、囊液及血清或血浆中的半乳糖凝集素-3浓度。分析从HGSC腹水及患者自身血液中分离的中性粒细胞,评估其预激活状态和活性氧生成。通过NK细胞、中性粒细胞和K562靶细胞(癌细胞系)体外共培养实验,评估NK细胞存活、脱颗粒及细胞毒作用。

HGSC患者囊液和腹水中的半乳糖凝集素-3水平较高。腹水中的中性粒细胞呈现预激活迹象,但患者样本之间的预激活程度差异很大。半乳糖凝集素-3可诱导部分患者腹水中性粒细胞产生活性氧,这与腹水中性粒细胞预激活状态的异质性一致。在NK细胞和K562靶细胞共培养体系中,观察到半乳糖凝集素-3诱导中性粒细胞产生的活性氧会降低NK细胞存活率并削弱抗肿瘤应答。

总之,研究结果显示HGSC肿瘤微环境中半乳糖凝集素-3水平较高。部分患者腹水中性粒细胞可能因半乳糖凝集素-3高水平而产生活性氧;中性粒细胞生成的活性氧进而可能调节NK细胞抗肿瘤免疫。本研究提示,应进一步评估靶向半乳糖凝集素-3的治疗能否用于卵巢癌。

展开英文摘要原文

High levels of Galectin-3 were observed in cyst fluid and ascites from patients with HGSC. Neutrophils present in HGSC ascites showed signs of priming; however, the priming status varied greatly among the patient samples. Galectin-3 induced production of reactive oxygen species in ascites neutrophils, but only from a fraction of the patient samples, which is in line with the heterogenous priming status of the ascites neutrophils. In co-cultures with NK cells and K562 target cells, we observed that Galectin-3-induced production of reactive oxygen species in neutrophils resulted in decreased NK cell viability and lowered anti-tumor responses.

Taken together, our results demonstrate high levels of Galectin-3 in the tumormicroenvironment of HGSC. High levels of Galectin-3 may induce production of reactiveoxygen species in ascites neutrophils in some patients. In turn, reactive oxygen species produced by neutrophils may modulate the NK cell anti-tumor immunity. Together, this study suggests further investigation to evaluate if a Galectin-3-targeting therapy may be used in ovarian cancer.

论文信息

作者
Karlsson V、Stål E、Stoopendahl E、Ivarsson A、Leffler H、Lycke M、Sundqvist M、Sundfeldt K
单位
Sahlgrenska Center for Cancer Research, University of Gothenburg, Gothenburg, Sweden.Sweden
文献类型
非美国政府资助研究
期刊
Frontiers in immunology2024
原文标识
PubMed 39759523 · DOI 10.3389/fimmu.2024.1506236