胃癌具有比其它肿瘤更明显的异质性，探索胃癌个体化治疗尤为重要。TCGA分子分型将胃癌分为4类，其中EBV相关胃癌有PI3KCA高频突变，CDKN2A甲基化，JAK2、PD-L1、PD-L2扩增，具有EBV来源特异性抗原表达特点，是免疫治疗极佳切入点，目前尚无反映该类细胞特征的研究模型与治疗策略。课题组前期建立了CTC检测平台及胃癌PDX研究模型，为此将1）结合肿瘤周边及外周血免疫细胞特征，分析预后相关免疫指标；2）基于原位肿瘤PDX模型及循环肿瘤细胞建立原代EBV相关胃癌模型；人源性免疫重建荷瘤小鼠模型；3）以上述EBV相关胃癌细胞和PDX模型筛选CDK4/6，JAK2等靶向抑制剂；促进病毒产生裂解的干预方案；4）以小鼠模型评价NK细胞治疗，EBV特异识别DC疫苗联合PD-1抗体的叠加疗效。本研究将为EBV相关胃癌提供精准治疗，有效解决胃癌高异质、疗效差难题，为肿瘤个性化治疗探索新途径。

Gastric cancer is one of the most common malignant tumors, possessing more obvious heterogeneity when comparing with other cancers. As a result, it is particularly necessary to conduct individualized treatment for gastric cancer. The TCGA molecular typing divide gastric cancer into four categories: EBVaGC, as one of the categories, have PI3KCA hypermutations,CDKN2A methylation, JAK2, PD-L1/2 amplification, and specific antigen expression characteristics from EBV. It’s the perfect entry points to the immunotherapy but now still no research model and treatment strategy. We have successfully built the CTC detection platform and the PDX model for gastric cancer, and we will: (1) analyzing Immune index that related to prognosis by connecting with immunology characteristic in adjacent tissues or peripheral blood of cancer;(2)constructing the Epstein-Barr virus-associated gastric cancer model in vitro and in vivo and human immune reconstitute animal model in tumor bearing mice basing on patient-derived tumor xenograft (PDX) and circulating tumor cell (CTC); (3) screening PI3K, CDK4/6, JAK2 targeted inhibitor through above-mentioned Epstein-Barr virus-associated gastric cancer cells and PDX model, and promoting the intervention plan to split the virus;(4)By establishing anthropogenic tumor-burdened model in mice, we'll evaluate the treatment with NK cells、EB virus's speciality in recognition vaccine-related to PD - L1 antibody and curative effect of double drug combination. The study will provide accurate treatment for EB virus associated gastric cancer, effectively solve problems about high heterogeneity and poor effects and explore new pathways for tumor individualized treatment.