| 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
|
| 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) |
