The spontaneous CD8+ T-cell response to HLA-A2-restricted NY-ESO-1b peptide in hepatocellular carcinoma patients Journal Article
| Authors: | Shang, X. Y.; Chen, H. S.; Zhang, H. G.; Pang, X. W.; Qiao, H.; Peng, J. R.; Qin, L. L.; Fei, R.; Mei, M. H.; Leng, X. S.; Gnjatic, S.; Ritter, G.; Simpson, A. J. G.; Old, L. J.; Chen, W. F. |
| Article Title: | The spontaneous CD8+ T-cell response to HLA-A2-restricted NY-ESO-1b peptide in hepatocellular carcinoma patients |
| Abstract: | 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)-γ and/or Granzyme B release by enzyme-linked immunospot (ELISPOT) assay and IFN-γ-productng intracellular cytokine flow cytomctry (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 × 104 CD8+ cells) and 1.2% as measured by IFN-γ 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-γ 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-stags 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. |
| Keywords: | adult; controlled study; human tissue; aged; middle aged; unclassified drug; human cell; major clinical study; liver cell carcinoma; carcinoma, hepatocellular; liver neoplasms; cancer staging; flow cytometry; cd8 antigen; antigen expression; t lymphocyte; cd8-positive t-lymphocytes; cancer immunotherapy; membrane proteins; in vitro study; peptide; tumor antigen; enzyme linked immunosorbent assay; granzyme b; immune response; genetic transfection; immunotherapy; antigens, neoplasm; serine endopeptidases; gamma interferon; cancer vaccines; antibody response; antigen recognition; peptide fragments; effector cell; melanoma antigen; immunoassay; protein family; cytokine release; enzyme linked immunospot assay; enzyme release; fluorescence activated cell sorting; antibody formation; lymphocyte function; tetramer; cell strain hepg2; hla a2 antigen; hla-a2 antigen; t lymphocyte antigen; granzymes; interferon type ii; humans; human; male; female; priority journal; article; ctp11 antigen; ny eso 1b peptide; scp 1 antigen; ssx antigen |
| Journal Title: | Clinical Cancer Research |
| Volume: | 10 |
| Issue: | 20 |
| ISSN: | 1078-0432 |
| Publisher: | American Association for Cancer Research |
| Date Published: | 2004-10-15 |
| Start Page: | 6946 |
| End Page: | 6955 |
| Language: | English |
| DOI: | 10.1158/1078-0432.ccr-04-0502 |
| PROVIDER: | scopus |
| PUBMED: | 15501973 |
| DOI/URL: | |
| Notes: | Clin. Cancer Res. -- Cited By (since 1996):48 -- Export Date: 16 June 2014 -- CODEN: CCREF -- Source: Scopus |
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