Abstract

B cells possess anti-tumor functions mediated by granzyme B, in addition to their role in antigen presentation and antibody production. However, the variations in granzyme B+ B cells between tumor and non-tumor tissues have been largely unexplored. Therefore, we integrated 25 samples from the Gene Expression Omnibus database and analyzed the tumor immune microenvironment. The findings uncovered significant inter- and intra-tumoral heterogeneity. Notably, single-cell data showed higher proportions of granzyme B+ B cells in tumor samples compared to control samples, and these levels were positively associated with disease-free survival. The elevated levels of granzyme B+ B cells in tumor samples resulted from tumor cell chemotaxis through the MIF- (CD74 + CXCR4) signaling pathway. Furthermore, the anti-tumor function of granzyme B+ B cells in tumor samples was adversely affected, potentially providing an explanation for tumor progression. These findings regarding granzyme B+ B cells were further validated in an independent clinic cohort of 40 liver transplant recipients with intrahepatic cholangiocarcinoma. Our study unveils an interaction between granzyme B+ B cells and intrahepatic cholangiocarcinoma, opening up potential avenues for the development of novel therapeutic strategies against this disease.

中文翻译：

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单细胞测序检测颗粒酶B+ B细胞与肝移植后肝内胆管癌患者的预后相关

摘要

B 细胞除了在抗原呈递和抗体产生中发挥作用外，还具有由颗粒酶 B 介导的抗肿瘤功能。然而，肿瘤组织和非肿瘤组织之间颗粒酶 B+ B 细胞的差异很大程度上尚未被探索。因此，我们整合了Gene Expression Omnibus数据库中的25个样本，并分析了肿瘤免疫微环境。研究结果揭示了肿瘤间和肿瘤内显着的异质性。值得注意的是，单细胞数据显示，与对照样本相比，肿瘤样本中颗粒酶 B+ B 细胞的比例更高，并且这些水平与无病生存呈正相关。肿瘤样本中颗粒酶 B+ B 细胞水平升高是肿瘤细胞通过 MIF- (CD74 + CXCR4) 信号通路趋化所致。此外，肿瘤样本中颗粒酶 B+ B 细胞的抗肿瘤功能受到不利影响，这可能为肿瘤进展提供解释。这些关于颗粒酶 B+ B 细胞的发现在由 40 名患有肝内胆管癌的肝移植受者组成的独立临床队列中得到了进一步验证。我们的研究揭示了颗粒酶 B+ B 细胞与肝内胆管癌之间的相互作用，为开发针对该疾病的新型治疗策略开辟了潜在途径。