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

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 TAAs were selected, and the expression of TAAs 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 TAAs 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)1₆₉₀ , P53₁₆₁ , multidrug resistance-associated protein (MRP)3₅₀₃ , Survivin2B₈₀ , melanoma-associated antigen (MAGE)-A4₁₄₃ , receptor tyrosine kinase ErbB-2/neu (Her2/neu)₆₃ , Wilms tumour (WT1)₂₃₅ , WT1₄₁₇ , β-catenin₂₉ , carcinoembryonic antigen (CEA)₂₆₈ , CEA₆₅₂ , epithelial cell adhesion molecule (EpCAM)₁₇₃ , enhancer of zeste homolog (EZH)2₂₉₁ , mucin 5AC (MUC5AC)₇₁₆ , glypican-3 (GPC3)₂₉₈ and kinesin family member 20A (KIF20A)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 TAAs may be promising for immunotherapy for cholangiocarcinoma, and patients with high lymphocyte counts may benefit more from immunotherapy.

Keywords: cholangiocarcinoma; enzyme-linked immunospot; immunotherapy; peptide vaccines.