CD80
免疫检查点
癌症研究
缺氧(环境)
免疫系统
免疫疗法
肿瘤微环境
A549电池
PD-L1
肺癌
生物
细胞
化学
免疫学
医学
细胞毒性T细胞
内科学
生物化学
体外
CD40
有机化学
氧气
作者
Achilleas Mitrakas,Alexandra Giatromanolaki,Michael I. Koukourakis
标识
DOI:10.1080/10799893.2023.2204944
摘要
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.
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