B细胞是肿瘤组织中数量丰富、但组成/功能研究非常少的重要免疫细胞。我们前期的工作证实：肝癌组织微环境既能募集具浆细胞分化潜能的B细胞，又可主动诱导具免疫调控功能、组织特异的B细胞亚群。有趣的是，我们近期还发现：肝癌中成熟B细胞（即浆细胞）的浸润程度显著的影响了髓系免疫微环境的组成与功能；而未成熟的B细胞也可有效的诱导出多种具很强炎性的T辅助细胞亚群。由此推测，B细胞既是组织微环境的重要组分，同时又塑造了组织免疫微环境的多样性。本项目拟以肝癌为模型，结合病理样本分析、高通量测序和实验模型，以期明确肝癌组织中B细胞的组成、来源及其生理病理意义；阐明不同的B细胞亚群对肝癌免疫微环境、对肝癌进展/退化的影响及其潜在的调控机制。相关研究不仅将揭示B细胞塑造肝癌组织免疫学特征的机制，更可为通过调控组织B细胞浸润与分化来重建或恢复其抗肿瘤功能提供理论基础。

B cells are prominent immune components of solid tumors, but their function and regulation are still largely unknown. We have previously shown that the hepatoma environments not only recruit the progenitor cells of plasma cells, but also induce tissue-resident regulatory B cells. More, our recent findings indicate that mature B cells play important roles in regulating the composition and function of myeloid signatures in human hepatoma, whereas the immature B cells are critical for the generation of inflammatory T cell environments. Based on these findings, we will combine the clinical sample analysis and experimental studies: 1) to investigate the distribution, phenotype and clinical significance of B cells in human hepatoma environments; 2) to study the underlying mechanisms and define the key molecules/pathways that regulate B cell differentiation in human hepatoma; 3) to explore the contribution and regulating mechanisms of B cells in the formation of tumor immune environment and their potential impact on targeted anti-tumor therapies. The results obtained from this project would not only reveal the novel mechanisms about B cell-related immune environments in human tumors, but would also provide the molecular basis for restore the anti-tumor immune microenvironments by selective modulating the accumulation and differentiation of B cell subsets.