Identification of HLA‑A*1101‑restricted cytotoxic Tlymphocyte epitopes derived from epidermal growth factor pathway substrate number 8.

Abstract

Epidermal growth factor receptor pathway substrate 8 (EPS8) is critical in the proliferation, progression and metastasis of solid and hematological types of cancer, and thus constitutes an ideal target for cancer immunotherapy. The present study aimed to identify human leukocyte antigen (HLA)-A*1101-restricted cytotoxic T lymphocyte (CTL) epitopes from EPS8 and characterize their immunotherapeutic efficacy in vitro. Two computer-based algorithms were used to predict native EPS8 epitopes with potential high binding affinity to the HLA-A*1101 molecule, which is the HLA-A allele with the highest frequency in the Chinese population. The peptide-induced cytokine production from the CTLs was examined using enzyme-linked immunosorbent spot analysis. The cytotoxic effects on cancer cells by CTLs primed with the identified peptides were examined using flow cytometry. A total of five peptides, designated as P380, P70, P82, P30 and P529, presented with high affinity towards the HLA-A*1101 molecule. In response to stimulation by these five peptides, enhanced secretion of interferon-γ from the CTLs and increased cytolytic capabilities of the CTLs toward cancer cells were noted, with the most potent effects observed from the P380 peptide. Taken together, the present study identified five potential CTL epitopes from EPS8. Among these, P380 presented with the highest therapeutic efficacy in vitro. These peptides may benefit the development of EPS8-based immunotherapy for the treatment of HLA-A*1101-positive hematological malignancies.