血清牛磺酸通过调节免疫微环境介导的肿瘤免疫逃逸来影响肺癌的进展。

Tu-Liang Liang, Hu-Dan Pan, Pei-Yu Yan, Jia-Ning Mi, Xiao-Cui Liu, Wei-Qian Bao, Li-Rong Lian, Cui-Fen Zhang, Ying Chen, Jing-Rong Wang, Ying Xie, Hua Zhou, Xiao-Jun Yao, Pawlec Graham, Elaine Lai-Han Leung, Liang Liu, Run-Ze Li
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引用次数: 0

摘要

简介牛磺酸是一种天然磺酸,参与各种生理和病理过程,如调节钙信号、免疫功能、炎症反应和细胞衰老。它具有预测肿瘤恶性转化和形成的潜力。我们之前的工作发现肺癌患者体内牛磺酸升高。然而,血清牛磺酸水平升高对肺癌进展的确切影响和机制,以及牛磺酸或含牛磺酸饮料对肺癌患者的适用性仍不清楚:我们的研究旨在系统研究牛磺酸在肺癌中的作用,最终目标是为肺癌治疗提供新策略:方法:应用肺癌 C57 小鼠和裸鼠模型、RNA 测序和稳定转染技术探讨牛磺酸对肺癌的影响和机制。收集太和医院2014年至2017年129例非小细胞肺癌(NSCLC)患者的组织进行免疫组化:结果:低剂量牛磺酸以及同等剂量的牛磺酸浸泡饮料能显著促进肺肿瘤生长。同样耐人寻味的是,牛磺酸对肺癌进展的促进作用随着剂量的增加而减弱。核因子红细胞 2-样 1(Nfe2l1 或 Nrf1)-活性氧(ROS)-PD-1 轴可能是牛磺酸在肺癌进展中发挥双重作用的潜在机制。然而,牛磺酸对肺癌进展和 Nfe2l1 抗肿瘤功能的影响主要取决于免疫能力。牛磺酸抑制肺癌生长可能是通过抑制 NF-κB 介导的裸鼠炎症反应,而不是通过影响 Nfe2l1 的功能。随着患者年龄的增加,Nfe2l1 基因和蛋白逐渐恢复到健康人的水平,但却失去了抗肺癌的作用:结论:牛磺酸是肺癌进展的潜在生物标志物,可预测预后不良和不适合特定患者。肺癌患者,尤其是年轻患者,应注意含牛磺酸饮料的潜在影响。相反,牛磺酸或其饮料可能更适合年长或免疫缺陷患者。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Serum taurine affects lung cancer progression by regulating tumor immune escape mediated by the immune microenvironment.

Introduction: Taurine is a naturally occurring sulfonic acid involved in various physiological and pathological processes, such as the regulation of calcium signaling, immune function, inflammatory response, and cellular aging. It has the potential to predict tumor malignant transformation and formation. Our previous work discovered the elevated taurine in lung cancer patients. However, the precise impact and mechanism of elevated serum taurine levels on lung cancer progression and the suitability of taurine or taurine-containing drinks for lung cancer patients remain unclear.

Objectives: Our study aimed to systematically investigate the role of taurine in lung cancer, with the ultimate goal of contributing novel strategies for lung cancer treatment.

Methods: Lung cancer C57 and nude mice models, RNA sequencing, and stable transfection were applied to explored the effects and mechanisms of taurine on lung cancer. Tissues of 129 non-small cell lung cancer (NSCLC) patients derived from 2014 to 2017 for immunohistochemistry were collected in Taihe Hospital.

Results: Low doses of taurine, as well as taurine-infused beverages at equivalent doses, significantly enhanced lung tumor growth. Equally intriguing is that the promoting effect of taurine on lung cancer progression wanes as the dosage increases. The Nuclear factor erythroid 2-like 1 (Nfe2l1 or Nrf1)-reactive oxygen species (ROS)-PD-1 axis may be a potential mechanism for dual role of taurine in lung cancer progression. However, taurine's impacts on lung cancer progression and the anti-tumor function of Nfe2l1 were mainly determined by the immune competence. Taurine inhitited lung tumor growth probably by inhibiting NF-κB-mediated inflammatory responses in nude mice rather than by affecting Nfe2l1 function. As patients age increased, Nfe2l1 gene and protein gradually returned to the levels observed in healthy individuals, but lost its anti-lung cancer effects.

Conclusions: Taurine emerges as a potential biomarker for lung cancer progression, predicting poor prognosis and unsuitability for specific patients. Lung cancer patients, especially young patients, should be conscious of potential effects of taurine-containing drinks. Conversely, taurine or its drinks may be more suitable for older or immune-deficient patients.

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