新抗原作为免疫治疗在国际上已经有多个临床研究报道其对晚期癌症的治疗效果。然而，目前还没有基础研究探究晚期NSCLC患者免疫治疗新抗原如何被树突细胞呈递给淋巴细胞，被免疫激活的淋巴细胞如何清除肿瘤细胞。本研究目的：1)建立免疫治疗疗效动物模型，在细胞层面上观测肿瘤特异性新抗原序列表达的树突细胞和患者的淋巴细胞共孵育时，树突细胞和淋巴细胞发生的改变。2）分析新抗原免疫治疗效果与潜在生物标志物TMB、MSI、新抗原负荷以及基因组甲基化水平的相关性。3）探究NSCLC患者新抗原的分布，分析免疫治疗疗效佳者新抗原及免疫细胞的分布特性。

Immunotherapy using patient cancer specific Neoantigens as a vaccine has been shown its exciting curative effect on several cancer types. Although exciting results from multiple clinical trials have encouraged more and more clinical investigators to pursue this therapeutic strategy, the underlying mechanism of how neoantigen be present by dendritic cells to lymphocytes and how active lymphocytes will kill cancers cells has not been reported yet. In this study, 1) we will use PDX mouse model, which is developed by our research group, to visualize the process of presentation of neoantigen by dendritic cells to lymphocytes in vitro. 2) In addition, we will analysis the relationship of the effect of active lymphocytes and biomarkers of TMB、MSI and DNA methylation. The observation results will provide laboratory evidence of how neoantigen immunotherapy is affected. 3) We will also investigate the distribution of specific neoantigens of NSCLC patients. These results will provide stratification for immunotherapy using patient specific neoantigens.