RRC ID 76470
Author Naoe M, Ogawa Y, Hasebe Y, Morita J, Shichijo T, Igarashi A, Fuji K, Iwamoto S, Suzuki T, Terao S.
Title Enhancement of IL-2-induced cytotoxicity by interferon-alpha in renal cell carcinoma.
Journal 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.
Volume 19(10-11)
Pages 479-86
Published 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
Human and Animal Cells VMRC-RCW(RCB1963)