The Spontaneous CD8 super(+) T-Cell Response to HLA-A2-Restricted NY-ESO-1b Peptide in Hepatocellular Carcinoma Patients

• Published in: Clinical cancer research 2004-10, Vol.10 (20), p.6946-6955
• Main Authors: Shang, Xiao-Ying, Chen, Hong-Song, Zhang, Hua-Gang, Pang, Xue-Wen, Qiao, Huan, Peng, Ji-Run, Qin, Li-Ling, Fei, Ran, Mei, Ming-Hui, Leng, Xi-Sheng, Gnjatic, Sacha, Ritter, Gerd, Simpson, Andrew JG, Old, Lloyd J, Chen, Wei-Feng
• Format: Article
• Language: English
• ISSN: 1078-0432

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 super(+) patients with NY-ESO-1 super(+) 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 super(+) T-cell responses to NY-ESO-1b in 28 NY-ESO-1 mRNA super(+)HLA-A2 super(+) HCC patients was 35.7% (10 of 28). The average magnitude of effector CD8 super(+) T cells was 0.3% (89 +/- 59 per 2.5 x 10 super(4) CD8 super(+) cells) and 1.2% as measured by IFN- gamma release ELISPOT and CytoSpot assays, respectively. These in vitro induced NY-ESO-1b-specific CD8 super(+) 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 super(+)CD8 super(+) T cells were also present. The CD8 super(+) T-cell response was apparently increased in patients with late-stage HCC. A discordance between antibody and CD8 super(+) T-cell responses in HCC patients was observed. CONCLUSIONS: The elevated frequency of specific CD8 super(+) T-cell responses to NY- ESO-1b in NY-ESO-1 mRNA super(+)HLA-A2 super(+) HCC patients suggests that NY-ESO-1 is appropriate for use in the immunotherapy of HCC patients.