胃癌患者肿瘤组织中B细胞的浸润及其免疫抑制功能的研究  

Infiltration and immunosuppressive function of tumor-associated B cells in gastric cancer patients

作　　者：李雨贤 段振铨 王莹 谭雪玲 余小红 张媛媛 朱宝行 邱远 彭六生[1] 邹全明[1] LI Yuxian;DUAN Zhenquan;WANG Ying;TAN Xueling;YU Xiaohong;ZHANG Yuanyuan;ZHU Baohang;QIU Yuan;PENG Liusheng;ZOU Quanming(Department of Microbiology and Biochemical Pharmacy,Faculty of Pharmacy and Laboratory Medicine,Army Medical University(Third Military Medical University),Chongqing,400038;Department of Oncology,Affiliated Hospital of North Sichuan Medical College,Nanchong,Sichuan Province,637000;Department of General Surgery,Second Affiliated Hospital,Army Medical University(Third Military Medical University),Chongqing,400037;College of Pharmacy,Chongqing University of Technology,Chongqing,400054,China)

机构地区：[1]陆军军医大学(第三军医大学)药学与检验医学系微生物与生化药学教研室,重庆400038 [2]川北医学院附属医院肿瘤科,四川南充637000 [3]陆军军医大学(第三军医大学)第二附属医院普外科,重庆400037 [4]重庆理工大学药学院,重庆400054

出　　处：《陆军军医大学学报》2024年第9期1034-1040,共7页Journal of Army Medical University

基　　金：重庆市自然科学基金面上项目(CSTC2021jcyj-msxmX0579)。

摘　　要：目的 检测B细胞在胃癌患者肿瘤组织和正常胃组织中的分布,分析其表型特征并探究肿瘤组织来源的B细胞对T细胞增殖的影响。方法 采用免疫组织化学染色对33例胃癌患者的肿瘤组织和正常胃组织切片进行B细胞表面标志CD19染色并分析其浸润数目,同时采用流式细胞术检测肿瘤组织和正常胃组织中B细胞的趋化因子受体和免疫球蛋白分子表达水平,并通过趋化实验研究CXCL12-CXCR4轴对B细胞的趋化作用,最后分离纯化出肿瘤组织和正常胃组织中的B细胞与自体的外周T细胞共培养,探讨B细胞对T细胞增殖的影响。结果 胃癌患者肿瘤组织中B细胞的浸润数目显著高于正常胃组织(P<0.01);且与正常胃组织来源的B细胞相比,肿瘤组织来源的B细胞高表达趋化因子受体CXCR4(P<0.05);TCGA数据库表明胃癌患者肿瘤组织中CXCL12的表达水平与CD19的表达水平呈正相关(r=0.15,P<0.01),胃癌患者临床样本的肿瘤组织中CXCL12的表达水平与B细胞浸润数目亦呈正相关(r=0.93,P<0.05),趋化实验证实CXCL12-CXCR4轴参与促进B细胞的趋化(P<0.05);尽管B细胞在肿瘤组织和正常胃组织中表达的IgM、IgG和IgA相当,但是体外共培养研究显示,与正常胃组织来源的B细胞相比,肿瘤组织来源的B细胞可显著抑制T细胞的增殖(P<0.01)。结论 B细胞在胃癌组织中的浸润增加,其可能通过CXCL12-CXCR4轴被募集至肿瘤组织,进而抑制T细胞的增殖以参与促进胃癌的进展。Objective To investigate the distribution of B cells in both tumor and non-tumor tissues of gastric cancer patients,analyze their phenotypic characteristics and explore the impact on T cell proliferation.Methods Immunohistochemical staining was utilized to detect the expression of B cell surface marker CD19 in tumor and non-tumor tissues from 33 gastric cancer patients.The expression levels of chemokine receptors and immunoglobulin molecules on B cells in both tumor and non-tumor tissues were measured using flow cytometry.Chemotaxis experiments were conducted to examine the role of the CXCL12-CXCR4 axis in B cell chemotaxis.B cells isolated and purified from both tissue types were co-cultured with autologous peripheral T cells to assess their effect on T cell proliferation.Results There were significantly more B cells infiltrated in tumor tissues than those infitrated in the non-tumor tissues of gastric cancer patients(P<0.01),and CXCR4 was highly expressed on tumor-infiltrating B cells compared with B cells derived from non-tumor tissues(P<0.05).The Cancer Genome Atlas(TCGA)analysis indicated that the expression level of CXCL12 in tumor tissues was positively correlated with the expression level of CD19 in gastric cancer patients(r=0.15,P<0.01).And the expression level of CXCL12 in tumor tissues of the gastric cancer patients was also positively correlated with the number of B cells infiltrated in tumor tissues.Chemotaxis experiments confirmed that the CXCL12-CXCR4 axis was involved in promoting B cell chemotaxis(P<0.05).Although B cells in tumor and non-tumor tissues had similar levels of IgM,IgG,and IgA expression,tumor-infiltrating B cells significantly inhibited the proliferation of T cells when compared with B cells derived from non-tumor tissues(P<0.01).Conclusion There are more B cells infiltrated in gastric cancer tissues,which may be recruited to tumor tissues through the CXCL12-CXCR4 axis,and then inhibit T cell proliferation to promote the progression of gastric cancer.

关 键 词：胃癌 B细胞 免疫抑制 

分 类 号：R392.12[医药卫生—免疫学] R730.23[医药卫生—基础医学] R735.2