. 2020 Oct 22;11:582657. doi: 10.3389/fimmu.2020.582657

Table 1.

Phenotypes and characteristics of tumor-associated Bregs.

Breg Type	Phenotype	Species	Location	Diseases or disease models	Characteristic	Reference
B10 Breg	CD19⁺CD24⁺CD38⁺	Human	Tumors and PB	Invasive breast cancer	Induce Tregs mediated by PD-L1	(31)
	CD19⁺CD5⁺CD1d⁺	Human	PB	Cervical cancer and cervical intraepithelial neoplasia	Inhibit perforin and GrB production by CD8⁺ T cells through IL-10, correlate with FIGO stages, the lymph node metastasis, the tumor differentiation, HPV infection, and the tumor metastasis	(36)
	CD19⁺CD24^hiCD38^hi	Human	Tumors and PB	GC	Inhibit IFN-γ and TNF-α by CD4⁺ Th cells through IL-10, induce Tregs through TGF-β1	(37)
	CD27⁺CD10^-	Human	Tumors and PB	GC	Decrease IFN-γ, TNF, and IL-17 expression by T cells through IL-10	(38)
GrB⁺ Breg	CD19⁺CD38⁺CD1d^hi IgM⁺CD147⁺	Human	Tumors	Breast, ovarian, cervical, colorectal, and prostate carcinomas	IL-21 induced, express GrB, inhibit T cell proliferation	(30)
TIM-1⁺ Breg	CD5^hiCD24⁻CD27^−/+CD38^+/hi	Human	Tumors and PB	HCC	Inhibit proliferation and TNF-α and IFN-γ production of CD8⁺ T cells, correlate with disease stage and poor survival	(39)
PD-1^hi Breg	CD5^hiCD24^−/+CD27^hi/+CD38^dim	Human	Tumors and PB	HCC	Result in decreased number and dysfunction of CD8⁺ T cells through IL-10, correlate with disease stage and early recurrence	(40)
PD-L1⁺ Breg	CD20⁺CD27^-	Human	PB	Melanoma	Suppress IFN-γ by T cells in a PD-L1-dependent manner	(41)
——	PD-1^-PD-L⁺CD19⁺	Mouse	Spleen and PB	4T1 breast cancer	Induced by MDSCs, inhibit proliferation and IFN-γ production by T cells	(42)
IgA⁺ Breg	IgA⁺CD19⁺	Mouse	Tumors	Colorectal tumor	Overexpress PD-L1, secrete IL-10 and TGF-β, inhibit proliferation and activation of CD8⁺ T cells	(43)
——	CD1d^hiCD5⁺	Mouse	Spleen	Burkitt-like lymphoma	Suppress CD20 mAb–induced lymphoma depletion and monocyte activation through IL-10	(44)
——	CD19⁺CD24^hiCD38^hi	Human	BM and PB	Multiple myeloma	Reduce NK cell-mediated lysis of MM cells	(45)
T2-MZP Breg	B220⁺CD23⁺IgM^hiCD21^hi	Mouse	TDLN	Melanoma	Preferentially accumulate in TDLNs, promote tumor growth in B-cell-deficient mice	(32)
——	CD19⁺IL10⁺	Human	Tumors	TSCC	Increased Bregs predict worse prognosis; induce Tregs	(46)
——	CD39⁺CD73⁺	Human	Tumors and PB	HNSCC	Suppress intracellular BTK and Ca2⁺ influx in effector B cells by secreting adenosine	(47)
——	CD19⁺CD24⁺CD38⁺	Human	Tumors and PB	HCC	Interact with liver cancer cells through the CD40/CD154 signaling pathway	(48)
——	CD19⁺CD24⁺CD38⁺	Human	BM and PB	AML	High frequency of Breg cells may predict poor AML prognosis.	(49)
——	CD19⁺CD24^hiCD27⁺	Human	Tumors and PB	GC	Inhibit proliferation and IFN-γ production by CD4⁺ T cells	(50)
——	CD19⁺CD81^hi CD25⁺	Mouse	Tumors	4T1 adenocarcinoma cells and B16F10 melanoma cells	Induce Tregs and decrease CD8⁺ T cells by TGF-β	(51)
——	CD1d^hiCD5⁺	Mouse	Tumors	PanIN	Regulated by BTK signaling, secrete IL-10 and IL-35	(52)
Plasmablast	CD19^loCD27^hi	Human	Tumors	Colorectal cancer	Gut-homing, inhibit T-cell IFN-γ and TNF-α expression but not promote Foxp3 expression	(53)

Breg, regulatory B cell; GrB, granzyme B; MDSC, myeloid-derived suppressor cell; MM, multiple myeloma; TDLN, tumor-draining lymph node; HNSCC, head and neck squamous cell carcinoma; HCC, hepatocellular carcinoma; HPV, human papillomavirus; TSCC, tongue squamous cell carcinoma; AML, acute myeloid leukemia; GC, gastric cancer; PB, peripheral blood; BM, bone marrow; BKT, Bruton’s tyrosine kinase; PanIN, pancreatic intra-epithelial neoplasia.