Immune responses against tumour‐associated antigen‐derived cytotoxic T lymphocyte epitopes in cholangiocarcinoma patients

摘要

Abstract Background & Aims Immunotherapy is a promising treatment option for cholangiocarcinoma. We compared cytotoxic T lymphocyte ( CTL ) responses against several tumour‐associated antigen ( TAA )‐derived epitopes in cholangiocarcinoma patients to identify candidate epitopes for immunotherapy. Methods Twenty‐six TAA s were selected, and the expression of TAA s in 6 cholangiocarcinoma cell lines and 9 specimens were measured using real‐time polymerase chain reaction ( PCR ). CTL responses against 38 TAA ‐derived epitopes were measured using samples from 26 cholangiocarcinoma patients by interferon‐γ enzyme linked immunospot ( ELISPOT )‐assay. Results Most TAA s were expressed in cholangiocarcinoma cell lines and specimens in PCR . Epitopes that stimulated a specific immune response were defined as those that elicited a CTL response in more than 3 patients and little response in healthy volunteers, as measured by ELISPOT ‐assay. Based on these criteria, there were 18 epitopes that stimulated specific immune responses: squamous cell carcinoma antigen recognized by T cells ( SART )1 690 , P53 161 , multidrug resistance‐associated protein ( MRP )3 503 , Survivin2B 80 , melanoma‐associated antigen ( MAGE )‐A4 143 , receptor tyrosine kinase ErbB‐2/neu (Her2/neu) 63 , Wilms tumour ( WT 1) 235 , WT 1 417 , β‐catenin 29 , carcinoembryonic antigen ( CEA ) 268 , CEA 652 , epithelial cell adhesion molecule (Ep CAM ) 173 , enhancer of zeste homolog ( EZH )2 291 , mucin 5 AC ( MUC 5 AC ) 716 , glypican‐3 ( GPC 3) 298 and kinesin family member 20A ( KIF 20A) 66 . Furthermore, the absolute number of lymphocytes in peripheral blood was significantly correlated with the TAA ‐specific response. Lastly, the overall survival was significantly prolonged in patients with 2 or more TAA ‐specific CTL responses compared with none to one. Conclusions These results demonstrated several TAA s may be promising for immunotherapy for cholangiocarcinoma, and patients with high lymphocyte counts may benefit more from immunotherapy.