| RRC ID |
76470
|
| 著者 |
Naoe M, Ogawa Y, Hasebe Y, Morita J, Shichijo T, Igarashi A, Fuji K, Iwamoto S, Suzuki T, Terao S.
|
| タイトル |
Enhancement of IL-2-induced cytotoxicity by interferon-alpha in renal cell carcinoma.
|
| ジャーナル |
Oncol Res
|
| Abstract |
Metastatic renal cell carcinoma (mRCC) treatment consists of molecular targeted agents and cytokines that have fundamentally different mechanisms of action. Clinical responses also differ; complete response is rare with molecular targeted agents but is sometimes achieved with cytokine therapies. Because of the relatively high efficacy of combination therapy with low-dose interleukin-2 (IL-2) and interferon-alpha (IFN-alpha) against mRCC, it is important to reevaluate cytokine therapies in vitro. Here, we show that when IL-2 is administered in combination with IFN-alpha, a stronger cytotoxic effect of PBMCs on RCC cell lines is observed than when IL-2 is administered alone. The upregulation of TNF-related apoptosis-inducing ligand on NK cell by IL-2 and suppression of regulatory T cells (Tregs) by IFN-alpha were recognized at the same time when cytotoxicity of peripheral blood mononuclear cells (PBMCs) was enhanced. IL-2 is known to activate natural killer cell cytotoxicity; however, IL-2 also stimulates Treg expansion, which enhances immunosuppression. On the other hand, IFN-alpha negatively regulates Treg cells, thereby increasing the function of immune effector cells. Our in vitro results may explain, at least in part, the clinical efficacy of combination low-dose IL-2 and IFN-alpha therapy against mRCC.
|
| 巻・号 |
19(10-11)
|
| ページ |
479-86
|
| 公開日 |
2011-1-1
|
| DOI |
10.3727/096504012x13285365944373
|
| PMID |
22715591
|
| MeSH |
Carcinoma, Renal Cell / drug therapy*
Cell Line, Tumor
Cytotoxicity, Immunologic
Drug Synergism
Humans
Interferon-alpha / pharmacology*
Interleukin-2 / pharmacology*
Kidney Neoplasms / drug therapy*
Killer Cells, Natural / immunology
Receptors, Interleukin-2 / genetics
Receptors, TNF-Related Apoptosis-Inducing Ligand / analysis
TNF-Related Apoptosis-Inducing Ligand / physiology
|
| IF |
4.949
|
| リソース情報 |
| ヒト・動物細胞 |
VMRC-RCW(RCB1963) |
