TABLE 1.

Human studies implicating Bregs dysregulation in cancer.

Cancer	Phenotype	Location	Breg function	Reference
HNSCC	CD19+CD39+CD73+	Tumor, blood	Breg population producing ADO. ADO inhibited BTK phosphorylation and calcium influx in effector B cells	[26]
	CD19+IL-10+	Tumor, lymph node	Bregs in tongue squamous cell carcinoma carried poor prognostic outcomes, and when co-cultured with T cells in vitro stimulated Treg formation	[27]
Hepatocellular carcinoma	CD19+CD24+CD38+	Tumor, blood	Increased circulating Bregs correlated with disease progression. Bregs promote HCC progression through CD40–CD154 interaction	[20]
	CD19+CD24+CD38+	Blood	Increased circulating Bregs in HCV-induced HCC is linked to poor prognosis and increased Tregs	[28]
	CD19+IL-10+TIM-1+	Tumor, blood	Increased IL-10 activity by Bregs in HCC. TIM-1+ Bregs downregulated CD4 cell production of granzyme A, B, and perforin	[29]
Gastric cancer	CD19+CD24hiCD27+	Tumor, blood	Bregs suppress CD4 proliferation and IFN-γ production	[30]
Ovarian cancer	CD19+IL-10+	Ascites	Ascites from ovarian tumor pts collected and enriched in Bregs. Co-cultured with CD8s and inhibited IFN-γ production	[21]
AML	CD19+IL-10+	Bone marrow, blood	Worse outcomes in AML associated with increased Bregs	[22]
Breast cancer	CD19+CD25+IL-10+	Tumor	Poor prognosis outcome. High coexistence of Bregs and Tregs	[24]
Cervical cancer	CD19+CD5+CD1d+	Tumor, blood	Bregs increased in cervical cancer, inhibit effector CD8 T cells from secreting perforin and granzyme B	[25]
Esophageal cancer	CD19+CD24hiCD27+	Blood	Circulating tumor exomes mediate Breg development	[31]

Abbreviations: ADO, adenosine; AML, acute myeloid leukemia; Breg, regulatory B cell; BTK, Bruton’s tyrosine kinase; HCC, hepatocellular carcinoma; HCV, hepatitis C virus; HNSCC, head and neck squamous cell cancer; IFN-γ, interferon-γ; Treg, regulatory T cell.