弥漫大B细胞淋巴瘤（DLBCL）是一组高度异质性的恶性肿瘤。基于精确分层和预后评估系统的个体化治疗使DLBCL大多能够被治愈。但仍有40%的DLBCL难以缓解或治疗后复发，提示仍有特殊的亚型未能被识别，用现有的治疗手段也难以治愈这些类型的淋巴瘤。申请人所在的项目组利用高通量的二代测序技术对200余例DLBCL进行了28个基因的基因突变和拷贝数分析，发现：免疫调控分子CD58的基因突变和拷贝数减少病例约占17.8%，这部分病例临床预后较差，成为具有独特标志的一大类型。而研究证实：CD58分子影响T细胞和NK细胞介导的抗肿瘤免疫。本课题将建立CD58突变的DLBCL模型和动物模型，探讨针对CD58基因异常弥漫大B细胞淋巴瘤，优化的嵌合抗原受体修饰的免疫细胞的治疗作用及其机制探索，为淋巴瘤的免疫治疗提供新的策略。

Diffuse large B cell lymphoma (DLBCL) is a group of highly heterogeneous disorders with differing morphology, biological behavior and clinical features. Base on accurate risk stratification and individualized therapy, it has become increasingly recognized that DLBCL is curable. However, 40% cases of DLBCL remained recurrent or relapsed after treatment,suggesting there are some special subtypes of DLBCL still not to be identified and it is also difficult to overcome this subtype DLBCL. Using next generation sequencing and copy number analysis ,17.8% cases of DLBCL were found mutation and reduced copy number of CD58 gene,resulting poor clinical outcome. Because CD58 gene encodes a molecule involved in T and natural killer cell-mediated responses,the NK and T cells mediated antitumor immune responses are influenced by the aberration of CD58 gene. This study will establish the animal model of DLBCL with CD58 mutation, We plan to explore the optimized chimeric antigen receptors modified immune cells for the treatment of this subtype DLBCL with CD58 aberration and to provide a new strategy for immunotherapy for lymphoma.