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学科主题: 基础医学
题名:
The spontaneous CD8(+) T-cell response to HLA-A2-restricted NY-ESO-1b peptide in hepatocellular carcinoma patients
作者: Shang, XY; Chen, HS; Zhang, HG; Pang, XW; Qiao, H; Peng, JR; Qin, LL; Fei, R; Mei, MH; Leng, XS; Gnjatic, S; Ritter, G; Simpson, AJG; Old, LJ; Chen, WF
刊名: CLINICAL CANCER RESEARCH
发表日期: 2004-10-15
卷: 10, 期:20, 页:6946-6955
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Oncology
研究领域[WOS]: Oncology
关键词[WOS]: TESTIS ANTIGEN NY-ESO-1 ; IMMUNE-RESPONSES ; CANCER-PATIENTS ; ANTIBODY-RESPONSES ; TUMOR IMMUNOLOGY ; DENDRITIC CELLS ; EXPRESSION ; GENES ; MAGE-1 ; IDENTIFICATION
英文摘要:

Purpose: Hepatocellular carcinoma (HCC) can express various cancer-testis antigens including NY-ESO-1, members of the SSX family, members of the MAGE family, SCP-1, and CTP11. Immunotherapy directed against these antigens is a potential alternative treatment for HCC. To date, it remains unclear whether HCC patients have spontaneous immune responses to these tumor antigens. The objectives of this study were to measure immune responses to NY-ESO-1, a promising cancer vaccine candidate, in HCC patients using the HLA-A2-restricted NY-ESO-1b peptide (p157-165) to measure cellular responses and whole protein to measure antibody responses.

Experimental Design: In HLA-A2(+) patients with NY-ESO-1(+) HCC, we analyzed T-cell antigen-dependent interferon (IFN)-gamma and/or Granzyme B release by enzyme-linked immunospot (ELISPOT) assay and IFN-gamma-producing intracellular cytokine flow cytometry (CytoSpot). As an assay independent of T-cell function, we performed tetramer staining. Antibodies to whole NY-ESO-1 were assayed by enzyme-linked immunosorbent assay.

Results: The frequency of specific CD8(+) T-cell responses to NY-ESO-1b in 28 NY-ESO-1 mRNA(+)HLA-A2(+) HCC patients was 35.7% (10 of 28). The average magnitude of effector CD8(+) T cells was 0.3% (89 +/- 59 per 2.5 X 10(4) CD8(+) cells) and 1.2% as measured by IFN-gamma release ELISPOT and CytoSpot assays, respectively. These in vitro induced NY-ESO-1b-specific CD8(+) T cells can also recognize HepG2 cells transfected with pcDNA3.1-NY-ESO-1 in both IFN-gamma and Granzyme B ELISPOT assays. Frequencies of NY-ESO-1b-specific T cells in several patients were confirmed by tetramer staining. Nonfunctional tetramer(+)CD8(+) T cells were also present. The CD8(+) T-cell response was apparently increased in patients with late-stage HCC. A discordance between antibody and CD8(+) T-cell responses in HCC patients was observed.

Conclusions: The elevated frequency of specific CD8(+) T-cell responses to NY-ESO-1b in NY-ESO-1 mRNA(+)HLA-A2(+) HCC patients suggests that NY-ESO-1 is appropriate for use in the immunotherapy of HCC patients.

语种: 英语
WOS记录号: WOS:000224627400023
Citation statistics:
内容类型: 期刊论文
版本: 出版稿
URI标识: http://ir.bjmu.edu.cn/handle/400002259/64967
Appears in Collections:基础医学院_免疫学系_期刊论文

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作者单位: 1.Guangxi Guilin Med Coll, Guilin, Guangxi Provinc, Peoples R China
2.Peking Univ, Hlth Sci Ctr, Sch Basic Med Sci, Dept Immunol, Beijing 100083, Peoples R China
3.Peking Univ, Hlth Sci Ctr, Peoples Hosp, Inst Hepatol, Beijing 100083, Peoples R China
4.Peking Univ, Hlth Sci Ctr, Peoples Hosp, Ctr Hepatobiliary Surg, Beijing 100083, Peoples R China
5.Mem Sloan Kettering Canc Ctr, New York Branch, Ludwig Inst Canc Res, New York, NY 10021 USA

Recommended Citation:
Shang, XY,Chen, HS,Zhang, HG,et al. The spontaneous CD8(+) T-cell response to HLA-A2-restricted NY-ESO-1b peptide in hepatocellular carcinoma patients[J]. CLINICAL CANCER RESEARCH,2004,10(20):6946-6955.
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