Detection of novel cancer-testis antigen-specific T-cell responses in TIL, regional lymph nodes, and PBL in patients with esophageal squamous cell carcinoma.
We recently identified three HLA-A2402-restricted epitope peptides derived from cancer-testis antigens (CTA), TTK protein kinase (TTK), lymphocyte antigen 6 complex locus K (LY6K), and insulin-like growth factor (IGF)-II mRNA binding protein 3 (IMP-3) for the development of immunotherapies against esophageal squamous cell carcinoma (ESCC). In order to evaluate their immunotherapeutic potential in ESCC patients, we estimated by ELISPOT assay the TTK-, LY6K-, or IMP-3-specific T-cell immune responses in tumor-infiltrating lymphocytes (TIL), regional lymph node lymphocytes (RLNL), and peripheral blood lymphocytes (PBL) expanded from 20HLA-A2402 (+) ESCC patients, and correlated their immune activity with the expression levels of TTK, LY6K, and IMP-3, and MHC class I in the tumors. Induction of TTK-antigen specific T-cell response in TIL to the peptide-pulsed target cells was detected in 14 out of 20 (70%) cases, while LY6K or IMP-3 specific T-cell activity was observed in 11 of 20 (55%) or in eight of 20 (40%) cases, respectively. Furthermore, T-cell activity in RLNL and PBL was detectable in the similar proportion of the 20 ESCC patients. Interestingly, CTA-specific T-cell immune response was found in 13 of 14 (93%) TIL obtained from ESCC tumors with strong MHC class I expression, while it could be observed only in two of six (33%) TIL from ESCC tumors with weak MHC class I expression. These results strongly suggest the pre-existence of specific T-cell responses to HLA-A24-restricted epitope peptides from TTK, LY6K, and IMP-3 in ESCC patients. Monitoring antigen-specific T-cell responses, as well as the expression levels of MHC class I and epitope CTA in tumors, should be a selection index for application of cancer vaccine therapies to the patients who are likely to show good immune response.
Mizukami
Yoshiki
Y
First Department of Surgery, University of Yamanashi, 1110 Shimokato, Chuo-city, Yamanashi 409-3898, Japan.
Kono
Koji
K
Daigo
Yataro
Y
Takano
Atsushi
A
Tsunoda
Takuya
T
Kawaguchi
Yoshihiko
Y
Nakamura
Yusuke
Y
Fujii
Hideki
H
D000368:Aged; D000950:Antigens, Ly / Q000032:analysis / Q000276:immunology*; D002294:Carcinoma, Squamous Cell / Q000276:immunology*; D018797:Cell Cycle Proteins / Q000032:analysis / Q000276:immunology*; D002460:Cell Line; D004938:Esophageal Neoplasms / Q000276:immunology*; D058851:GPI-Linked Proteins; D015395:Histocompatibility Antigens Class I / Q000032:analysis; D006801:Humans; D008198:Lymph Nodes / Q000276:immunology*; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000032:analysis / Q000276:immunology*; D017346:Protein Serine-Threonine Kinases / Q000032:analysis / Q000276:immunology*; D011505:Protein-Tyrosine Kinases; D016601:RNA-Binding Proteins / Q000032:analysis / Q000276:immunology*
D000950:Antigens, Ly; D018797:Cell Cycle Proteins; D058851:GPI-Linked Proteins; D015395:Histocompatibility Antigens Class I; C498780:IGF2BP3 protein, human; C525725:LY6K protein, human; D009363:Neoplasm Proteins; D016601:RNA-Binding Proteins; D011505:Protein-Tyrosine Kinases; D017346:Protein Serine-Threonine Kinases; C075840:TTK protein, human