論文 - 詳細
| RRC ID | 67012 |
|---|---|
| 著者 | Saito R, Miki Y, Abe T, Miyauchi E, Abe J, Nanamiya R, Inoue C, Sato I, Sasano H. |
| タイトル | 11β hydroxysteroid dehydrogenase 1: a new marker for predicting response to immune-checkpoint blockade therapy in non-small-cell lung carcinoma. |
| ジャーナル | Br J Cancer |
| Abstract |
BACKGROUND:Understanding the status of intratumoural immune microenvironment is necessary to ensure the efficacy of immune-checkpoint (IC) blockade therapy. Cortisol plays pivotal roles in glucocorticoid interactions in the immune system. We examined the correlation between intratumourally synthesised cortisol through 11β hydroxysteroid dehydrogenase (HSD) 1 and the immune microenvironment in non-small-cell lung carcinoma (NSCLC). METHODS:We correlated 11βHSD1 immunoreactivity in 125 cases of NSCLC with the amount of intratumoural immune cells present, and 11βHSD1 immunoreactivity with the efficacy of IC blockade therapy in 18 specimens of NSCLC patients. In vitro studies were performed to validate the immunohistochemical examination. RESULTS:11βHSD1 immunoreactivity showed a significant inverse correlation with the number of tumour-infiltrating lymphocytes and CD3- or CD8-positive T cells. 11βHSD1 immunoreactivity tended to be inversely correlated with the clinical efficacy of the IC blockade therapy. In vitro studies revealed that 11βHSD1 promoted the intratumoural synthesis of cortisol. This resulted in a decrease in cytokines and in the inhibition of monocyte migration. CONCLUSIONS:Our study is the first report clarifying the inhibitory effects of intratumourally synthesised cortisol through 11βHSD1 on immune cell migration. We propose that the response to IC blockade therapy in NSCLC may be predicted by 11βHSD1. |
| 巻・号 | 123(1) |
| ページ | 61-71 |
| 公開日 | 2020-7-1 |
| DOI | 10.1038/s41416-020-0837-3 |
| PII | 10.1038/s41416-020-0837-3 |
| PMID | 32336752 |
| PMC | PMC7341889 |
| MeSH | 11-beta-Hydroxysteroid Dehydrogenase Type 1 / genetics* Aged Aged, 80 and over Biomarkers, Tumor / genetics* CD8-Positive T-Lymphocytes / drug effects CD8-Positive T-Lymphocytes / immunology Carcinoma, Non-Small-Cell Lung / genetics* Carcinoma, Non-Small-Cell Lung / immunology Carcinoma, Non-Small-Cell Lung / pathology Carcinoma, Non-Small-Cell Lung / therapy Female Humans Immune Checkpoint Inhibitors / administration & dosage* Immune Checkpoint Inhibitors / immunology Male Middle Aged Tumor Microenvironment / drug effects |
| IF | 5.791 |
| リソース情報 | |
| ヒト・動物細胞 | PC-9(RCB4455) RERF-LC-AI(RCB0444) |