研究动态
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CD19 CD73 B 细胞浸润表明胃癌预后不良以及对免疫治疗的不利反应。

CD19+CD73+ B cells infiltration indicates poor prognosis and unfavorable responses to immunotherapy in gastric cancer.

发表日期:2024 Aug 29
作者: Yawei Zhang, Wendong Wang, Qi Liu, Jianwu Jiang, Peng Zhao, Changjun Huang, Yingying Li, Yang Fu
来源: INTERNATIONAL IMMUNOPHARMACOLOGY

摘要:

分化簇 73 (CD73) 在免疫细胞上表达,通过抑制抗肿瘤免疫在肿瘤抑制中发挥重要作用。本研究的目的是探讨胃癌(GC)患者B细胞上CD73的表达和功能机制。通过双重免疫组化染色评估390例GC患者中CD19 CD73 B细胞的预后意义。采用流式细胞术分析 8 名 GC 患者的新鲜肿瘤和非肿瘤组织样本的 CD19 亚群的表型。在 scRNA-seq 队列中还对 CD19 CD73 B 细胞进行了生物信息学分析,并使用多重免疫荧光染色评估了 CD19 B 细胞亚型。观察到胃癌 (GC) 组织中 CD19 CD73 B 细胞的浸润升高与正常组织相比。在 GC 中,高 CD19 CD73 B 细胞浸润、较差的总体生存率和对新辅助免疫治疗的反应性降低之间存在很强的相关性。这些细胞作为调节性 B 细胞 (Breg) 的新子集出现,与腺苷代谢和 CD8 T 细胞的耗竭有关。 CD19 CD73 B 细胞还与免疫抑制细胞因子 IL-10 和 TGFB1 的产生相关。进一步分析表明 CD19 CD73 B 细胞与晚期 GC 之间存在关联。GC 中 CD19 CD73 B 细胞的存在可作为临床结果的预后指标和对新辅助免疫治疗反应不佳的预测标记。 CD19 CD73 B 细胞的存在和 CD8 T 细胞耗竭以及免疫抑制之间的相关性突出了这些细胞的促肿瘤功能。版权所有 © 2024。由 Elsevier B.V 出版。
Cluster of Differentiation 73 (CD73) is expressed on immune cells and plays a significant role in tumor inhibition by suppressing antitumor immunity. The objectives of this study were to explore the expression and functional mechanisms of CD73 on B cells in patients with gastric cancer (GC).The prognostic significance of CD19+CD73+ B cells was evaluated in 390 GC patients through dual immunohistochemistry staining. Flow cytometry was employed to analyze the phenotype of the CD19 subpopulation using fresh tumor and non-tumor tissue samples from 8 GC patients. A bioinformatics analysis of CD19+CD73+ B cells was also performed within the scRNA-seq cohort, and the CD19+ B cell subtype was assessed using multiple immunofluorescence staining.The infiltration of CD19+CD73+ B cells was observed to be elevated in gastric cancer (GC) tissue compared to normal tissues. A strong correlation was observed between high CD19+CD73+ B cell infiltration, poor overall survival, and diminished responsiveness to neoadjuvant immunotherapy in GC. These cells emerged as a novel subset of regulatory B cells (Bregs) linked to adenosine metabolism and the exhaustion of CD8+ T cells. The CD19+CD73+ B cells also correlated with the production of immunosuppressive cytokines IL-10 and TGFB1. Further analysis indicated an association between CD19+CD73+ B cells and advanced-stage GC.The presence of CD19+CD73+ B cells in GC may serve as a prognostic indicator for clinical outcomes and a predictive marker for poor responsiveness to neoadjuvant immunotherapy. The correlation between the presence of CD19+CD73+ B cells and CD8+ T cell exhaustion, along with immunosuppression, highlights the tumor-promoting function of these cells.Copyright © 2024. Published by Elsevier B.V.