論文 - 詳細
| RRC ID | 68819 |
|---|---|
| 著者 | Mimura K, Kua LF, Shiraishi K, Kee Siang L, Shabbir A, Komachi M, Suzuki Y, Nakano T, Yong WP, So J, Kono K. |
| タイトル | Inhibition of mitogen-activated protein kinase pathway can induce upregulation of human leukocyte antigen class I without PD-L1-upregulation in contrast to interferon-γ treatment. |
| ジャーナル | Cancer Sci |
| Abstract |
Recently, we reported that human leukocyte antigen (HLA) class I expression is predominantly regulated by the mitogen-activated protein kinase (MAPK) pathway as one of the oncogenic regulations of HLA class I expression. In the present study, we examined mechanisms of how HLA class I and PD-L1 are regulated by MAPK inhibitors and interferon-γ (IFN-γ). Furthermore, we evaluated the expression of major signal transduction molecules by Western blot and anti-tumor CTL activity by a cytotoxic assay when HLA class I and PD-L1 were modulated by MAPK inhibitors and/or IFN-γ. As a result, we confirmed, as a more general phenomenon, that the inhibition of MAPK could upregulate HLA class I expression in a panel of human solid tumors (n = 26). Of note, we showed that MAPK inhibitors act on the upregulation of HLA class I expression through a different pathway from IFN-γ; there was an additive effect in the upregulation of HLA class I when treated with the combination of MAPK inhibitors and IFN-γ, and there was no overlapping activation of JAK2/STAT1 and Erk1/2 molecules when treated with either IFN-γ or MAPK inhibitors. Furthermore, we showed that IFN-γ-treatment impaired the tumor-specific CTL activity due to the upregulation of PD-L1 in spite of the upregulation of HLA class I, while MAPK inhibitors can augment the tumor-specific CTL activity due to the upregulated HLA class I without PD-L1 alterations. In conclusion, in addition to the original anti-proliferative activity, MAPK inhibitors may work toward the enhancement of T-cell-mediated anti-tumor immunity through the upregulation of HLA class I without the upregulation of PD-L1. |
| 巻・号 | 105(10) |
| ページ | 1236-44 |
| 公開日 | 2014-10-1 |
| DOI | 10.1111/cas.12503 |
| PMID | 25154680 |
| PMC | PMC4462358 |
| MeSH | B7-H1 Antigen / analysis B7-H1 Antigen / physiology* Cell Line, Tumor Flavonoids / pharmacology Histocompatibility Antigens Class I / physiology* Humans Interferon-gamma / pharmacology* Killer Cells, Natural / immunology MAP Kinase Signaling System / drug effects MAP Kinase Signaling System / physiology* T-Lymphocytes, Cytotoxic / immunology Up-Regulation |
| IF | 4.966 |
| 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 | 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 | TE-1(RCB2100) TE-4(RCB2097) TE-5(RCB1949) TE-14(RCB2101) PC-9(RCB4455) |