| 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
|
| リソース情報 |
| ヒト・動物細胞 |
C2C12(RCB0987)
B16F10(RCB2630) |
