College of Life Sciences, University of Chinese Academy of Sciences, Beijing 100049, China; BGI-Shenzhen, Shenzhen 518083, China.
BGI-Shenzhen, Shenzhen 518083, China; China National GeneBank, BGI-Shenzhen, Shenzhen 518120, China.
Cell Immunol. 2022 Jul;377:104537. doi: 10.1016/j.cellimm.2022.104537. Epub 2022 May 14.
Neoantigens are attractive targets for cancer immunotherapy. The identification of neoantigens shared by different patients could promote the broad application of neoantigen-based immunotherapy. This study aimed to investigate shared neoantigens in esophageal carcinoma. By combining a comprehensive analysis of mutation data of 722 patients with esophageal carcinoma (EC) and in silico neoantigen prediction, we obtained 216 recurrent neoantigen candidates predicted to bind to high-frequency class I human leukocyte antigen (HLA) alleles. We further performed immunogenicity validation tests on five high-frequency HLA-A*0201 binding neoantigens derived from TP53 mutations. The results demonstrated that the peptides p53 H193R, R248Q, and R273H could efficiently prime peptide-specific CD8 T cells to secrete IFN-γ and lyse mutant peptide-pulsed T2 cells. In conclusion, we obtained a group of shared neoantigen candidates in esophageal carcinoma and validated the immunogenicity of three novel TP53 neoantigens. These peptides might be potential targets for immunotherapy.
新抗原是癌症免疫治疗的有吸引力的靶点。鉴定不同患者之间共享的新抗原可以促进基于新抗原的免疫治疗的广泛应用。本研究旨在研究食管癌中的共享新抗原。通过对 722 例食管癌（EC）患者的突变数据进行综合分析和基于计算机的新抗原预测，我们获得了 216 个预测与高频 HLA Ⅰ类分子结合的复发性新抗原候选物。我们进一步对源自 TP53 突变的 5 个高频 HLA-A*0201 结合新抗原进行了免疫原性验证测试。结果表明，肽 p53 H193R、R248Q 和 R273H 能够有效地刺激肽特异性 CD8 T 细胞分泌 IFN-γ并溶解突变肽脉冲的 T2 细胞。总之，我们获得了一组食管癌共享的新抗原候选物，并验证了三个新的 TP53 新抗原的免疫原性。这些肽可能是免疫治疗的潜在靶点。
