論文 - 詳細
| RRC ID | 68849 |
|---|---|
| 著者 | Kawana S, Saito R, Miki Y, Kimura Y, Abe J, Sato I, Endo M, Sugawara S, Sasano H. |
| タイトル | Suppression of tumor immune microenvironment via microRNA-1 after epidermal growth factor receptor-tyrosine kinase inhibitor resistance acquirement in lung adenocarcinoma. |
| ジャーナル | Cancer Med |
| Abstract |
Immunotherapy is considered one of the most important therapeutic strategies for patients with lung adenocarcinoma after the development of epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) resistance. However, useful predictors of immunotherapy for these patients has not been examined well, although the status of the tumor immune microenvironment (TIME), including programmed death-ligand 1 expression and lymphocyte infiltration, has been generally known to provide predictive markers for the efficacy of immunotherapy. This study aimed to clarify novel predictors of immunotherapy following EGFR-TKI resistance in lung adenocarcinoma, especially regarding micro RNA (miRNA). We evaluated the correlation between EGFR-TKI resistance and lymphocyte infiltration, before and after acquiring EGFR-TKI resistance, in 21 cases of lung adenocarcinoma, and further explored this by in vitro studies, using miRNA PCR arrays. Subsequently, we transfected miRNA-1 (miR-1), the most variable miRNA in this array, into three kinds of lung cancer cells, and examined the effects of miR-1 on EGFR-TKI sensitivity, cytokine expression and lymphocyte migration. Histopathological examination demonstrated that infiltration levels of CD8-positive T cells were significantly decreased after development of EGFR-TKI resistance. In vitro studies revealed that miR-1 significantly inhibited EGFR-TKI effect and induction of cytokines, such as C-C motif chemokine ligand 5 and C-X-C motif chemokine ligand 10, causing inhibition of monocyte migration. These results indicate that the upregulated miR-1 might suppress the TIME, following development of EGFR-TKI resistance. Therefore, miR-1 could be a clinically useful marker to predict therapeutic efficacy of immunotherapy in lung adenocarcinoma patients with EGFR-TKI resistance. |
| 巻・号 | 10(2) |
| ページ | 718-727 |
| 公開日 | 2021-1-1 |
| DOI | 10.1002/cam4.3639 |
| PMID | 33305905 |
| PMC | PMC7877390 |
| MeSH | Adenocarcinoma of Lung / drug therapy Adenocarcinoma of Lung / genetics Adenocarcinoma of Lung / immunology* Adenocarcinoma of Lung / pathology Aged Aged, 80 and over Biomarkers, Tumor / genetics Drug Resistance, Neoplasm* ErbB Receptors / antagonists & inhibitors Female Follow-Up Studies Gene Expression Regulation, Neoplastic Humans Lung Neoplasms / drug therapy Lung Neoplasms / genetics Lung Neoplasms / immunology* Lung Neoplasms / pathology Male MicroRNAs / genetics* Middle Aged Prognosis Protein Kinase Inhibitors / pharmacology* Tumor Cells, Cultured Tumor Microenvironment / immunology* |
| IF | 3.491 |
| 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 | News |
| 各媒体での言及数の合計 | 2 |
| 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 | PC-9(RCB4455) |