Immunogenicity of Del19 EGFR mutations in Chinese patients affected by lung adenocarcinoma
Immunogenicity of Del19 EGFR mutations in Chinese patients affected by lung adenocarcinoma
复制标题
中国肺腺癌患者中 Del19 EGFR 突变的免疫原性
DOI：
10.1186/s12865-019-0320-1
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发表时间：
2019-11-13
期刊：
影响因子：
3
通讯作者：
Lou，Yanyan
中科院分区：
文献类型：
--
作者：
Pan，Deng;Zhou，Dapeng;Lou，Yanyan
背景由癌细胞呈递的突变肽是比自身肽更优越的上级疫苗候选物。突变型K-Ras、P53和EGFR（表皮生长因子受体）肽作为癌症疫苗在胰腺癌、结肠直肠癌和肺癌中的功效已被测试。EGFR Del 19突变在中国肺腺癌患者中常见，其免疫原性尚不清楚。结果用NetMHC软件预测中国肺腺癌患者EGFR Del 19突变的HLA结合表位。采用酶联免疫吸附试验（ELISA）检测肺癌患者血清中EGFR反应性IgG。Del 19突变可由多种HLA I类分子呈现，其中delE746_A750在中国人群中呈现率为37.5%。对于HLA II类分子，EGFR的Del 19突变可能由多种HLA-DRB 1分子呈递，其中delE746_A750在中国人群中占58.1%。EGFR基因Del 19突变患者血清中野生型EGFR蛋白的反应性显著高于EGFR L 858 R点突变患者和EGFR野生型gene.ConclusionsThese findings suggest，EGFR的Del 19突变在中国肺腺癌患者中的发生率估计为40%，可作为中国肺癌患者免疫治疗的独特靶点。
BackgroundMutant peptides presented by cancer cells are superior vaccine candidates than self peptides. The efficacy of mutant K-Ras, P53 and EGFR (Epidermal Growth Factor Receptor) peptides have been tested as cancer vaccines in pancreatic, colorectal, and lung cancers. The immunogenicity of EGFR Del19 mutations, frequent in Chinese lung adenocarcinoma patients, remains unclear.ResultsWe predicted the HLA binding epitopes of Del19 mutations of EGFR in Chinese lung adenocarcinoma patients with NetMHC software. Enzyme-linked immunosorbent assay (ELISA) was performed to detect the EGFR-reactive IgG in lung cancer patients. Del19 mutations may be presented by multiple HLA Class I molecules, with delE746_A750 presented by 37.5% of Chinese population. For HLA Class II molecules, Del19 mutations of EGFR may be presented by multiple HLA-DRB1 molecules, with delE746_A750 presented by 58.1% of Chinese population. Serum reactivity to wild type EGFR protein was significantly higher in patients with Del19 EGFR mutations than those with EGFR L858R point mutation or with EGFR wild type genotype.ConclusionsThese findings suggest that Del19 mutations of EGFR, with an estimated frequency of 40% in Chinese lung adenocarcinoma patients, may serve as unique targets for immunotherapy in Chinese lung cancer patients.