Zhou Si, Liu Songming, Zhao Lijian, Sun Hai-Xi
College of Life Sciences, University of Chinese Academy of Sciences, Beijing, China.
College of Medical Technology, Hebei Medical University, Shijiazhuang, China.
Front Oncol. 2022 Mar 21;12:786438. doi: 10.3389/fonc.2022.786438. eCollection 2022.
Neoantigens are mutated antigens specifically generated by cancer cells but absent in normal cells. With high specificity and immunogenicity, neoantigens are considered as an ideal target for immunotherapy. This study was aimed to investigate the signature of neoantigens in breast cancer. Somatic mutations, including SNVs and indels, were obtained from cBioPortal of 5991 breast cancer patients. 738 non-silent somatic variants present in at least 3 patients for neoantigen prediction were selected. (38%), the highly mutated gene in breast cancer, could produce the highest number of neoantigens per gene. Some pan-cancer hotspot mutations, such as E545K (6.93%), could be recognized by at least one HLA molecule. Since there are more SNVs than indels in breast cancer, SNVs are the major source of neoantigens. Patients with hormone receptor-positive or HER2 negative are more competent to produce neoantigens. Age, but not the clinical stage, is a significant contributory factor of neoantigen production. We believe a detailed description of breast cancer neoantigen signatures could contribute to neoantigen-based immunotherapy development.
新抗原是癌细胞特异性产生但在正常细胞中不存在的突变抗原。由于具有高特异性和免疫原性，新抗原被认为是免疫治疗的理想靶点。本研究旨在探究乳腺癌中新抗原的特征。体细胞突变，包括单核苷酸变异（SNV）和插入缺失，来自5991例乳腺癌患者的cBioPortal。选择了至少在3例患者中存在的738个非同义体细胞变异用于新抗原预测。乳腺癌中高度突变的基因（占38%）每个基因产生的新抗原数量最多。一些泛癌热点突变，如E545K（6.93%），可被至少一种HLA分子识别。由于乳腺癌中SNV比插入缺失更多，因此SNV是新抗原的主要来源。激素受体阳性或HER2阴性的患者产生新抗原的能力更强。年龄而非临床分期是新抗原产生的重要影响因素。我们相信对乳腺癌新抗原特征的详细描述有助于基于新抗原的免疫治疗发展。
