Identification of HLA‑A*1101‑restricted cytotoxic T lymphocyte epitopes derived from epidermal growth factor pathway substrate number 8.
Identification of HLA‑A*1101‑restricted cytotoxic T lymphocyte epitopes derived from epidermal growth factor pathway substrate number 8.
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源自表皮生长因子途径底物 8 号的 HLA-A1101 限制性细胞毒性 T 淋巴细胞表位的鉴定
DOI：
10.3892/mmr.2016.5888
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发表时间：
2016-12
影响因子：
3.4
通讯作者：
Li Y
中科院分区：
文献类型：
--
作者：
Lu H;Tang B;He Y;Zhou W;Qiu J;Li Y
表皮生长因子受体途径底物8（Epidermal growth factor receptor pathway substrate 8，EPS 8）在实体肿瘤和血液肿瘤的增殖、进展和转移中起着重要作用，是肿瘤免疫治疗的理想靶点。本研究旨在鉴定EPS 8的人类白细胞抗原（HLA）-A*1101限制性细胞毒性T淋巴细胞（CTL）表位，并表征其体外免疫效力。使用两种基于计算机的算法来预测对HLA-A*1101分子具有潜在高结合亲和力的天然EPS 8表位，HLA-A*1101分子是中国人群中频率最高的HLA-A等位基因。使用酶联免疫吸附斑点分析法检查从CTL的肽诱导的细胞因子产生。使用流式细胞术检查用鉴定的肽引发的CTL对癌细胞的细胞毒性作用。共5个肽，命名为P380，P70，P82，P30和P529，对HLA-A*1101分子具有高亲和力。响应于这五种肽的刺激，注意到CTL的干扰素-γ分泌增强和CTL对癌细胞的细胞溶解能力增加，其中从P380肽观察到最有效的作用。总之，本研究确定了五个潜在的CTL表位从EPS 8。其中，P380在体外表现出最高的治疗效果。这些肽可能有利于开发用于治疗HLA-A*1101阳性血液恶性肿瘤的基于EPS 8的免疫疗法。
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.