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