Department of Respiratory and Critical Care Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Department of Respiratory and Critical Care Medicine, Peking University People's Hospital, Beijing, China.
Front Immunol. 2022 Mar 9;12:749461. doi: 10.3389/fimmu.2021.749461. eCollection 2021.
Immune checkpoint inhibitors (ICIs) have recently emerged as an important option for treating patients with advanced non-small cell lung cancer (NSCLC). Neoantigens are important biomarkers and potential immunotherapy targets that play important roles in the prognosis and treatment of patients with NSCLC. This study aimed to evaluate and characterize the relationships between somatic mutations and potential neoantigens in specimens from patients who underwent surgical treatment for NSCLC.
This prospective study evaluated specimens from patients with NSCLC who underwent surgical treatment at the Peking Union Medical College, China, from June 2019 to September 2019. Whole-exome sequencing was performed for tumor tissues and corresponding normal tissues. Candidate neoantigens were predicted using generative software, and the relationships between various mutation characteristics and number of neoantigens were evaluated.
Neoantigen-related gene mutations were less frequent than mutations affecting the whole genome. Genes with high neoantigen burden had more types and higher frequencies of mutations. The number of candidate neoantigens was positively correlated with missense mutations, code shift insertions/deletions, split-site variations, and nonsense mutations. However, in the multiple linear regression analysis, only missense mutations were positively correlated with the number of neoantigens. The number of neoantigens was also positively correlated with base transversions (A>C/C>A, T>G/G>T, and C>G/G>C) and negatively correlated with base transitions (A>G/G>A and C>T/T>C).
The number of candidate neoantigens in NSCLC specimens was associated with mutation frequency, type of mutation, and type of base substitution.
免疫检查点抑制剂（ICIs）最近已成为治疗晚期非小细胞肺癌（NSCLC）患者的重要选择。新抗原是重要的生物标志物和潜在的免疫治疗靶点，在 NSCLC 患者的预后和治疗中发挥着重要作用。本研究旨在评估和描述接受 NSCLC 手术治疗患者标本中的体细胞突变与潜在新抗原之间的关系。
本前瞻性研究评估了 2019 年 6 月至 9 月在中国北京协和医学院接受手术治疗的 NSCLC 患者的标本。对肿瘤组织和相应的正常组织进行全外显子组测序。使用生成软件预测候选新抗原，并评估各种突变特征与新抗原数量之间的关系。
新抗原相关基因的突变频率低于影响全基因组的突变频率。具有高新抗原负担的基因具有更多类型和更高频率的突变。候选新抗原的数量与错义突变、编码移码插入/缺失、分裂位点变异和无义突变呈正相关。然而，在多元线性回归分析中，只有错义突变与新抗原数量呈正相关。新抗原的数量也与碱基颠换（A>C/C>A、T>G/G>T 和 C>G/G>C）呈正相关，与碱基转换（A>G/G>A 和 C>T/T>C）呈负相关。
NSCLC 标本中的候选新抗原数量与突变频率、突变类型和碱基取代类型有关。
