Open AccessDetection of novel cancer‐testis antigen‐specific T‐cell responses in TIL, regional lymph nodes, and PBL in patients with esophageal squamous cell carcinoma
Author(s) -
Mizukami Yoshiki,
Kono Koji,
Daigo Yataro,
Takano Atsushi,
Tsunoda Takuya,
Kawaguchi Yoshihiko,
Nakamura Yusuke,
Fujii Hideki
Publication year - 2008
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/j.1349-7006.2008.00844.x
Subject(s) - elispot , antigen , immune system , epitope , t cell , tumor infiltrating lymphocytes , lymph node , immunology , major histocompatibility complex , cancer research , mhc class i , biology , medicine , cd8
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. ( Cancer Sci 2008; 99: 1448–1454)