我们在前期已观察到：在肝癌和消化道肿瘤组织中，多种免疫细胞或因子可呈现出各自独特的表型与分布，并对疾病进展起着不同甚至相反的作用。B细胞是肿瘤组织中数量丰富但亚群/功能研究非常空白的重要免疫细胞。我们新近发现：肝癌组织微环境主动募集或诱导出多个具“促肿瘤”活性的B细胞亚群来促进疾病进展。但是相关促肿瘤亚群在肠癌组织减少甚至缺乏，B细胞主要起限制肠癌进展的作用。提示：不同肿瘤组织微环境对B细胞亚群募集、极化以及功能有不同的影响机制。本课题拟结合人体样本检测和实验模型，来系统的研究/比较：B细胞在肝癌与肠癌组织微环境中聚集、亚群极化与功能的差异与调控机制；筛选并鉴定出可用于判断肝癌和肠癌进展/退化的B细胞亚群或功能分子；并探讨选择性调控B细胞在组织中聚集与分化的可行性以及对肿瘤进展的影响；为肿瘤免疫治疗提供新的思路和干预靶点。

We and others have previously shown that the infiltrated immune cells and cytokines could exhibit distinct phenotype and distribution patterns in human tumors originated from liver and digestive tract, and thus have differential or even opposing impact on disease progression. B cells are prominent immune components of solid tumors, but their function and regulation are still largely unknown. We recently observed that several types of B cells were recruited or induced by hepatoma microenvironments and subsequently promoted disease progression. In contrast, these identified protumorigenic B cells were reduced and even lacking in colorectal cancer. B cell majority exhibited functions that inhibited colorectal cancer progression. These results indicate that the local conditions from different cancer microenvironments may influence the accumulation and functional programs of B cells. Based on these findings, we will combine the clinical sample analysis and experimental studies to: 1) characterize the accumulation, composition and functional activities of B cell subsets in both liver cancer and colorectal tumor tissues, and dissect the underlying mechanisms; 2) screen and define the key subsets and signaling molecules that may have significant impact on the progression or degeneration of liver or colorectal cancer; 3) evaluate the effectiveness on tumor progression by selectively regulating the recruitment and differentiation of B cell subset in liver colorectal tumor tissues. The results obtained from this project will not only reveal the molecular mechanisms by which tumor induce the generation of B cell subset, but also provide the molecular basis for the development of B cells as novel target for cancer prevention and cure.