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1.400038 重庆,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
2.637000 四川 南充,川北医学院附属医院肿瘤科
3.400037 重庆,陆军军医大学(第三军医大学)第二附属医院普外科
4.400054 重庆, 重庆理工大学药学院
[彭六生,E-mail:pengliusheng06@163.comPENG Liusheng, E-mail: pengliusheng06@163.com
[邹全明,E-mail:qmzou@tmmu.edu.cnZOU Quanming, E-mail: qmzou@tmmu.edu.cn
收稿:2023-10-26,
修回:2023-11-24,
纸质出版:2024-05-15
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李雨贤, 段振铨, 王莹, 等. 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[J]. 陆军军医大学学报, 2024,46(9):1034-1040.
Yuxian LI, Zhenquan DUAN, Ying WANG, et al. Infiltration and immunosuppressive function of tumor-associated B cells in gastric cancer patients[J]. Journal of Army Medical University, 2024, 46(9): 1034-1040.
李雨贤, 段振铨, 王莹, 等. 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[J]. 陆军军医大学学报, 2024,46(9):1034-1040. DOI: 10.16016/j.2097-0927.202312006.
Yuxian LI, Zhenquan DUAN, Ying WANG, et al. Infiltration and immunosuppressive function of tumor-associated B cells in gastric cancer patients[J]. Journal of Army Medical University, 2024, 46(9): 1034-1040. DOI: 10.16016/j.2097-0927.202312006.
目的
2
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
2
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
2
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
2
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
2
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
2
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
2
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
2
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.
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