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

Yuxian LI; Zhenquan DUAN; Ying WANG; Xueling TAN; Xiaohong YU; Yuanyuan ZHANG; Baohang ZHU; Yuan QIU; Liusheng PENG; Quanming ZOU

doi:10.16016/j.2097-0927.202312006

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

Clinical Medicine | 更新时间：2026-01-09

- Infiltration and immunosuppressive function of tumor-associated B cells in gastric cancer patients
- Journal of Army Medical University Vol. 46, Issue 9, Pages: 1034-1040(2024)
- 作者机构：
  
  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
- 作者简介：
- 基金信息：
  
  the General Project of Natural Science Foundation of Chongqing(CSTC2021jcyj-msxmX0579)
- DOI：10.16016/j.2097-0927.202312006
  CLC： R392.12;R730.23;R735.2
- Received：26 October 2023，
  
  Revised：2023-11-24，
  
  Published：15 May 2024
- 稿件说明：
移动端阅览
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：

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.

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(

＜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(

＜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(

=0.15，

＜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(

=0.93，

＜0.05)，趋化实验证实CXCL12-CXCR4轴参与促进B细胞的趋化(

＜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(

＜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。

Abstract

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 (

0.01)

and CXCR4 was highly expressed on tumor-infiltrating B cells compared with B cells derived from non-tumor tissues (

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 (

=0.15

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 (

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 (

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

Keywords

references

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