| 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
|
| リソース情報 |
| ヒト・動物細胞 |
A549,
RERF-LC-KJ(RCB1313)
LC-2/ad(RCB0440) |
