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Expression of multidrug resistance-associated protein 3 and cytotoxic T cell responses in patients with hepatocellular carcinoma.

Abstract：

BACKGROUND/AIMS:Multidrug resistance-associated protein 3 (MRP3) is a carrier-type transport protein belonging to the ABC transporters. It is expressed in normal tissues, and enhanced expression in many cancers has been reported. In this study, we investigated the usefulness of MRP3 as a target antigen in immunotherapy for hepatocellular carcinoma (HCC). METHODS:The MRP3 expression level in HCC tissue was measured by quantitative PCR. MRP3-specific T cell responses were investigated by several immunological techniques using peripheral blood mononuclear cells or tumor-infiltrating lymphocytes. RESULTS:The MRP3 expression level in HCC tissue was significantly higher than that in non-cancerous tissue (P<0.05). MRP3-specific cytotoxic T cells (CTLs) could be induced regardless of liver function, the presence or absence of HCV infection, the blood AFP level, and the stage of HCC. The CTLs showed cytotoxicity against HCC cells overexpressing MRP3. A negative correlation was present between the MRP3 expression level in HCC tissue and the frequency of MRP3-specific CTLs. The frequency of MRP3-specific CTLs increased after HCC treatment, such as transcatheter arterial embolization and radiofrequency ablation. CONCLUSIONS:Our study demonstrates that MRP3 is a potential candidate for tumor antigen with strong immunogenicity in HCC immunotherapy.

journal_name

J Hepatol

journal_title

Journal of hepatology

authors

Mizukoshi E,Honda M,Arai K,Yamashita T,Nakamoto Y,Kaneko S

doi

10.1016/j.jhep.2008.05.012

subject

Has Abstract

pub_date

2008-12-01 00:00:00

pages

946-54

issue

6

eissn

0168-8278

issn

1600-0641

pii

S0168-8278(08)00356-5

journal_volume

49

pub_type

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