Expression of multidrug resistance-associated protein 3 and cytotoxic T cell responses in patients with hepatocellular carcinoma.
OBJECTIVE
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.
Mizukoshi
Eishiro
E
Department of Gastroenterology, Graduate School of Medicine, Kanazawa University, Kanazawa, Ishikawa 920-8641, Japan.
Honda
Masao
M
Arai
Kuniaki
K
Yamashita
Tatsuya
T
Nakamoto
Yasunari
Y
Kaneko
Shuichi
S
D000368:Aged; D001706:Biopsy; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D006528:Carcinoma, Hepatocellular / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D045744:Cell Line, Tumor; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D015972:Gene Expression Regulation, Neoplastic / Q000276:immunology; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D007371:Interferon-gamma / Q000276:immunology; D008099:Liver / Q000473:pathology; D008113:Liver Neoplasms / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000235:genetics* / Q000276:immunology*; D012333:RNA, Messenger / Q000378:metabolism; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
D007371:Interferon-gamma; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D012333:RNA, Messenger; C114462:multidrug resistance-associated protein 3