非小细胞肺癌（NSCLC）是人类中最致命的肿瘤之一。免疫检查点抑制剂（ICIs）的免疫治疗革命性地改变了晚期疾病患者的治疗。肿瘤微环境条件，如缺氧和低 PH 值，可能会损害ICIs的有效性。我们报告了缺氧和酸性对A549和H1299 NSCLC细胞系中主要检查点分子PD-L1、CD80和CD47的表达水平的影响。缺氧诱导PD-L1蛋白和mRNA表达，抑制CD80 mRNA水平，并增强IFNβ蛋白表达。当细胞暴露于酸性条件时，反应相反。缺氧诱导CD47分子的蛋白和mRNA水平升高。结论是，缺氧和酸性是PD-L1和CD80免疫检查点分子表达的重要调节因子。酸性有助于抑制干扰素类型 I 通路。这些研究结果表明，缺氧和酸性通过直接影响癌细胞呈现免疫检查点分子和释放类型 I 干扰素的能力来支持癌细胞逃避免疫监视。针对缺氧和酸性可能会增强NSCLC中ICIs的活性。

Non-small cell lung cancer (NSCLC) is one of the most lethal tumors in humans. Immunotherapy with immune checkpoint inhibitors (ICIs) has revolutionized the treatment of patients with advanced diseases. Tumor microenvironment conditions like hypoxia and low pH may compromise the efficacy of ICIs.We report the effect of hypoxia and acidity on the expression levels of the major checkpoint molecules, namely PD-L1, CD80, and CD47, in the A549 and H1299 NSCLC cell lines.Hypoxia induces PD-L1 protein and mRNA expression, represses CD80 mRNA levels, and enhances IFNβ protein expression. An opposite effect was noticed when cells were exposed to acidic conditions. Hypoxia-induced the CD47 molecule at protein and mRNA levels. It is concluded that hypoxia and acidity are important regulators of the expression of PD-L1 and CD80 immune checkpoint molecules. Acidity contributes to the suppression of the interferon type I pathway.These findings suggest that hypoxia and acidity assist cancer cells in the escape from immune surveillance through direct effects on cancer cells' ability to present immune checkpoint molecules and release type I interferons. Targeting hypoxia and acidity may enhance the activity of ICIs in NSCLC.