論文 - 詳細
| RRC ID | 67890 |
|---|---|
| 著者 | Mori D, Tsujikawa T, Sugiyama Y, Kotani SI, Fuse S, Ohmura G, Arai A, Kawaguchi T, Hirano S, Mazda O, Kishida T. |
| タイトル | Extracellular acidity in tumor tissue upregulates programmed cell death protein 1 expression on tumor cells via proton-sensing G protein-coupled receptors. |
| ジャーナル | Int J Cancer |
| Abstract |
Acidity in the tumor microenvironment has been reported to promote cancer growth and metastasis. In this study, we examined a potential relation between extracellular acidity and expression level of the immune checkpoint molecule PD-L1 in murine squamous cell carcinoma (SCC) and melanoma cell lines. PD-L1 expression in the tumor cells was upregulated by culturing in a low pH culture medium. Tumor-bearing mice were allowed to ingest sodium bicarbonate, resulting in neutralization of acidity in the tumor tissue, a decrease in PD-L1 expression in tumor cells, and suppression of tumor growth in vivo. Proton-sensing G protein-coupled receptors (GPCRs), T cell death-associated gene 8 (TDAG8) and ovarian cancer G-protein-coupled receptor 1 (OGR1), were upregulated by low pH, and essentially involved in the acidity-induced elevation of PD-L1 expression in the tumor cells. Human head and neck SCC RNAseq data from the Cancer Genome Atlas also suggested a statistically significant correlation between expression levels of the proton sensors and PD-L1 mRNA expression. These findings strongly suggest that neutralization of acidity in tumor tissue may result in reduction of PD-L1 expression, potentially leading to inhibition of an immune check point and augmentation of anti-tumor immunity. |
| 巻・号 | 149(12) |
| ページ | 2116-2124 |
| 公開日 | 2021-12-15 |
| DOI | 10.1002/ijc.33786 |
| PMID | 34460096 |
| MeSH | Animals B7-H1 Antigen / genetics* B7-H1 Antigen / metabolism Cell Line, Tumor / transplantation Datasets as Topic Disease Models, Animal Female Gene Expression Regulation, Neoplastic / immunology Humans Hydrogen-Ion Concentration Mice Neoplasms / genetics Neoplasms / immunology* Neoplasms / pathology Protons RNA-Seq Receptors, G-Protein-Coupled / metabolism* Tumor Escape / genetics Tumor Microenvironment / genetics Tumor Microenvironment / immunology Up-Regulation |
| IF | 5.145 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 4 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| ヒト・動物細胞 | C2C12(RCB0987) B16F10(RCB2630) |