論文 - 詳細
| RRC ID | 63503 |
|---|---|
| 著者 | Okita R, Yukawa T, Nojima Y, Maeda A, Saisho S, Shimizu K, Nakata M. |
| タイトル | MHC class I chain-related molecule A and B expression is upregulated by cisplatin and associated with good prognosis in patients with non-small cell lung cancer. |
| ジャーナル | Cancer Immunol Immunother |
| Abstract |
MHC class I chain-related molecule A and B (MICA/B) are NK group 2 member D (NKG2D) ligands, which are broadly expressed in transformed cells. Both DNA damage-induced ataxia-telangiectasia-mutated (ATM)- and ATM and Rad3-related protein kinases (ATM-ATR) signaling and oncogene-induced PI3K-AKT signaling regulate the expression of NKG2D ligands, which promote NK cell-mediated cytotoxicity via NKG2D-NKG2D ligand interactions. NKG2D ligand overexpression was recently reported to be correlated with good prognosis in several types of cancer. However, the prognostic significance of NKG2D ligands in non-small cell lung cancer (NSCLC) remains unclear. Here, MICA/B expression was evaluated based on immunohistochemistry of 91 NSCLC samples from patients following radical surgery. In addition, expression of MICA/B was assessed in NSCLC cell lines treated with cisplatin in order to evaluate the regulatory mechanisms of MICA/B expression. Overall, 28 out of 91 (30.8%) specimens showed high expression level of MICA/B, which was associated with low (18)F-fluorodeoxyglucose uptake and manifestation of adenocarcinoma. After a median follow-up of 48.2 months, high MICA/B expression was associated with good recurrence-free survival (p = 0.037). In vitro assays using cell lines revealed that MICA/B expression was upregulated by cisplatin via ATM-ATR signaling, resulting in enhanced NK cell-mediated cytotoxicity. Upregulated MICA/B expressions in patients with radically resected NSCLC are predictive of good disease prognosis. Cisplatin-induced MICA/B upregulation is possibly an indirect mechanism by which the innate immune system eliminates tumor cells. NKG2D-NKG2D ligand-targeting therapy is a promising avenue for future immune-chemotherapy development. |
| 巻・号 | 65(5) |
| ページ | 499-509 |
| 公開日 | 2016-5-1 |
| DOI | 10.1007/s00262-016-1814-9 |
| PII | 10.1007/s00262-016-1814-9 |
| PMID | 26940474 |
| MeSH | Adult Aged Aged, 80 and over Antineoplastic Agents / pharmacology Ataxia Telangiectasia Mutated Proteins / genetics Ataxia Telangiectasia Mutated Proteins / metabolism Carcinoma, Non-Small-Cell Lung / genetics Carcinoma, Non-Small-Cell Lung / metabolism* Carcinoma, Non-Small-Cell Lung / pathology Cell Line, Tumor Cell Proliferation / drug effects Cell Proliferation / genetics Cisplatin / pharmacology* Female Histocompatibility Antigens Class I / biosynthesis* Humans Immunohistochemistry Kaplan-Meier Estimate Killer Cells, Natural / drug effects Killer Cells, Natural / metabolism Lung Neoplasms / genetics Lung Neoplasms / metabolism* Lung Neoplasms / pathology Male Middle Aged Prognosis RNA Interference Signal Transduction / drug effects Signal Transduction / genetics Up-Regulation / genetics* |
| IF | 5.442 |
| 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 | 3 |
| 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 | LC-2/ad(RCB0440) A549, RERF-LC-KJ(RCB1313) |