Detection of glypican-3-specific CTLs in chronic hepatitis and liver cirrhosis

Hayashi, Yasuhiro

doi:10.3892/or_00000418

Cited by 9 publications

(9 citation statements)

References 25 publications

(35 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Although evidence of immune response to these two antigens in HCC patients has been demonstrated, eliciting antitumor immunity using these two antigens is still not robust. 18-21 One of the potential explanations is that the expression of these two proteins during embryogenesis may have caused immune tolerance in adults. However, it is still unclear how the host immunosurvillence mechanisms interact with HCC to allow tumor to grow.…”

Section: Introductionmentioning

confidence: 99%

Kinase inhibitor Sorafenib modulates immunosuppressive cell populations in a murine liver cancer model

Cao

Youn

et al. 2011

Laboratory Investigation

113

View full text Add to dashboard Cite

Accumulating evidence suggests that regulatory T cells (Tregs) and myeloid-derived suppressor cells (MDSC) are elevated in cancer patients and tumor-bearing hosts, and that depletion of Tregs and MDSC may enhance the anti-tumor immunity of the host. Sorafenib, a novel multikinase inhibitor, is approved for the treatment of several human cancers including advanced hepatocellular carcinoma (HCC). Sorafenib is believed to inhibit tumor growth via anti-angiogenesis, cell cycle arrest, and inducing apoptosis. However, the impact of Sorafenib on immune cell populations in tumor-bearing hosts is unclear. In this report, we show that Tregs and MDSC are increased in the spleens and bone marrows of the BALB/c mice with liver hepatoma. The increase in Tregs and MDSCs was positively correlated with tumor burden. Treatment of Sorafenib not only inhibited HCC cell growth in the mice, but also significantly decreased the suppressive immune cell populations: Tregs and MDSCs. In conclusion, our study strongly suggests that Sorafenib can enhance antitumor immunity via modulating immunosuppressive cell populations in the murine liver cancer model.

show abstract

Section: Introductionmentioning

confidence: 99%

Kinase inhibitor Sorafenib modulates immunosuppressive cell populations in a murine liver cancer model

Cao

Youn

et al. 2011

Laboratory Investigation

113

View full text Add to dashboard Cite

show abstract

“…Hayashi et al, quantified the number of GPC3-specific CTLs in the peripheral blood of patients with either chronic hepatitis or liver cirrhosis [44]. They selected patients who were HCV-RNA (+) or HBs antigen (+) within 6 months prior to the study for which no HCC nodules were detected by radiologic imaging.…”

Section: Immunotherapeutic Gpc3 Vaccinementioning

confidence: 99%

Therapeutic Potential of Targeting Glypican-3 in Hepatocellular Carcinoma

Allegretta¹,

Filmus²

2011

ACAMC

View full text Add to dashboard Cite

Glypican-3 (GPC3) is a developmentally-regulated oncofetal protein that has been established as a clinically-relevant biomarker for early hepatocellular carcinoma (HCC). It is one of the first transcripts to appear during malignant hepatocyte transformation, and is expressed at the protein level in approximately half of high-grade dysplastic macronodules in cirrhotic liver. Several studies show it is expressed in most (75 to 100%) of HCCs confirmed by histopathology. The protein is anchored to the hepatocyte membrane by a glycosyl-phosphatidylinositol (GPI) anchor and shows consistent membrane immunostaining pattern, making it a viable target for immunotherapeutic approaches. Targeting GPC3 for therapeutic intervention is a promising approach for the clinical management of HCC and selected other tumors that express the marker.

show abstract

“…We previously reported that 39% of HCC patients had detectable GPC3-specific CTLs by a direct ex vivo IFN-γ ELIsPOT assay (25). In this study, GPC3-specific CTLs were detectable before treatment in 11 of 27 patients (41%).…”

Section: Discussionmentioning

confidence: 60%

Radiofrequency ablation for hepatocellular carcinoma induces glypican-3 peptide-specific cytotoxic T lymphocytes

et al. 2011

View full text Add to dashboard Cite

Abstract. Glypican-3 (GPC3), a carcinoembryonic antigen, is an ideal target for anticancer immunotherapy against hepatocellular carcinoma (HCC). In this study, we attempted to compare the induction of the GPC3-specific T-cell-mediated immune response after locoregional therapies in HCC patients and tumor-bearing mice. Twenty-seven HCC patients treated with locoregional therapies, including radiofrequency ablation (RFA), surgical resection and transcatheter arterial chemoembolization (TACE), were prospectively enrolled in this study. Additionally, we performed RFA experiments using a mouse model. GPC3-specific T-cell response was investigated pretreatment and post-treatment by an interferon-γ enzyme-linked immunospot assay using peripheral blood mononuclear cells from HCC patients and lymph node cells from tumor-bearing mice. Circulating GPC3-specific cytotoxic T lymphocytes (CTLs) were increased in 5 of 9 patients after RFA and in 4 of 9 patients after TACE, but in only 1 of 9 patients after surgical resection. All 7 patients with GPC3-expressing HCCs exhibited an increase in GPC3-specific CTLs after RFA or TACE, whereas none of the 7 patients did after surgical resection. The number of increased GPC3-specific CTLs after RFA was significantly larger than that after surgical resection (P= 0.023). Similarly, the frequency of GPC3-specific CTLs after RFA was significantly greater than that after surgical resection in the mouse model (P=0.049). We validated for the first time the stronger effect on the immune system brought by RFA compared with surgical resection for HCC patients and tumor-bearing mice. Combined treatment of RFA and immunotherapy is a reasonable strategy against HCC. IntroductionHepatocellular carcinoma (HCC) is one of the most common and most serious cancers worldwide (1). Locoregional therapies, including radiofrequency ablation (RFA), surgical resection, and transcatheter arterial chemoembolization (TACE), are recognized as the gold-standard therapies for HCC patients whose cancer lesions are limited to the liver (2). However, the recurrence rate remains quite high despite potentially curative treatment (3,4). The reasons for this are as follows: first, a multicentric new tumor frequently occurs from underlying active hepatitis or cirrhosis and, second, a small tumor undetectable by imaging modalities frequently exists before treatment and would be left untreated (5). Therefore, the establishment of effective adjuvant therapy to prevent recurrence is urgently required, and Radiofrequency ablation for hepatocellular carcinoma induces glypican-3 peptide-specific cytotoxic T lymphocytes

show abstract

Detection of glypican-3-specific CTLs in chronic hepatitis and liver cirrhosis

Cited by 9 publications

References 25 publications

Kinase inhibitor Sorafenib modulates immunosuppressive cell populations in a murine liver cancer model

Kinase inhibitor Sorafenib modulates immunosuppressive cell populations in a murine liver cancer model

Therapeutic Potential of Targeting Glypican-3 in Hepatocellular Carcinoma

Radiofrequency ablation for hepatocellular carcinoma induces glypican-3 peptide-specific cytotoxic T lymphocytes

Contact Info

Product

Resources

About