TABLE 9.

The controversial immune cell type in cancer: B cells.

Cells	The research direction	Result	Reference
B cells	Prognostic marker	CD20 B cells, naive B cells, and CD27 isotypic transformed memory B cells are independent prognostic factors for survival in HCC. During the progression of HCC, intratumoral infiltration of B cells is significantly impaired. High density of tumor-infiltrating B cells means better clinical outcome.	Zhang et al. (2019)
B cells	The immune mechanism	In mice with HCC, B cell depletion blocked the production of these macrophages, increased anti-tumor T cell response, and reduced HCC growth. This pathway is involved in the increased expression of DNA methyltransferase 1 and EZH2 in HCC and HCC cells.	Wei et al. (2019)
B cells	Prognostic marker	Tumor derived exosome-activated B cells strongly express Tim-1 protein and have inhibitory activity against CD8 T cells. Exogenous HMGB1 activates B cells and promotes the expansion of Tim-1 Breg cells through Toll-like receptor (TLR) 2/4 and mitogen-activated protein kinase (MAPK) signaling pathways. Accumulation of TIM-1BREG cells in tumors is associated with advanced disease, early recurrence, and reduced survival in HCC patients.	Ye et al. (2018)
B cells	The immune mechanism	In MDR2 mice, CD20 B cell ablation promoted age-mediated fibrosis regression and inhibited the tumorigenic TNFα/NF-κB pathway.	Faggioli et al. (2018)
B cells	The immune mechanism	B cells and IgG2 may play an important role in the inhibition of liver tumorigenesis. Hepatocellular specific expression of ras oncogene may play a role in the inhibition of B cells, and B cells and T cells may be inhibited in developing liver tumors.	Wang et al. (2017)
B cells	The immune mechanism	CCL20 derived from tumor cells interacts with CD19CD5 B cells overexpressed by CCR6 to promote the development of HCC, possibly through enhanced angiogenesis.	He et al. (2017)
B cells	Prognostic marker	More than 50% of B cells in HCC exhibit FcγRII-activated phenotypes, and the production of FcγRII-activated B cells may represent a mechanism through which immune activation is associated with immune tolerance in the tumor environment.	Ouyang et al. (2016)
B cells	The immune mechanism	A novel oncogenic PD-1(HI) B cell subtype has been identified in human HCC that exhibits a phenotype distinct from that of surrounding regulatory B cells. TLR4-mediated upregulation of BCL6 is critical for inducing PD-1(HI) B cells, which act through an IL10-dependent pathway after interacting with PD-L1, thereby causing T cell dysfunction and promoting disease progression.	Xiao et al. (2016)
B cells	Prognostic marker	Tumor infiltrating T cells and B cells are in close contact with each other, and their density is associated with superior survival in patients with HCC.	Garnelo et al. (2017)
B cells	The immune mechanism	Selective recruitment of CXCR3 (+) B cells Bridges the pro-inflammatory interleukin-17 response and the polarization of tumorigenic macrophages in the tumor environment, and blocking the migration or function of CXCR3 (+) B cells may contribute to the defeat of HCC.	Liu et al. (2015)
B cells	The immune mechanism	After liver MET transfection, TUNEL (+) hepatocytes were increased in B cell-or macrophage-deficient mice, suggesting that these cells provide a protective effect against MET-induced hepatocyte apoptosis.	Subleski et al. (2015)
B cells	The immune mechanism	An increase in intrahepatic B cells at the edge of the tumor was positively associated with tumor invasion characteristics and more tumor recurrence. Bregs directly interact with HCC cells through the CD40/CD154 signaling pathway, thereby promoting the growth and aggressiveness of HCC.	Shao et al. (2014)
B cells	The immune mechanism	As a trans activator, HBx can regulate the activated B nuclear factor kappa-light chain enhancer (NF-κB) and transcription factor AP-2. HBx may cause the loss of apoptotic function, or directly contribute to carcinogenesis by realizing the transformation function, and accelerate the development of HCC.	Zhang et al. (2014)
B cells	The immune mechanism	Activation-induced cytidine deaminase (AID) acts as genomic mutants in activated B cells, and inappropriate expression of AID is associated with immunopathological phenotypes of human B cell malignancies. Abnormal activation of AID in hepatocytes leads to the accumulation of multiple genetic changes in the p53 gene, which may enhance genetic susceptibility to mutagenesis leading to HCC development.	Kou et al. (2007)