. 2023 Oct 5;14:1233085. doi: 10.3389/fimmu.2023.1233085

Table 1.

Breg cell phenotypes discovered in human cancer.

Breg cell	Phenotype	Cancer	Location	Expressed molecules	Description
B10 Breg	CD19⁺CD24⁺CD38⁺	Invasive breast cancer	Tumor tissues, PBMCs	IL-10	PD-L1 mediated induction of Treg cells (47).
		Hepatocellular carcinoma	Tumor tissues, PBMCs	IL-10	Induce tumor proliferation and invasion via CD40/CD154 signaling pathway (48).
		Acute myeloid lymphoma	Bone marrow, PBMCs	IL-10	Increased Breg cells are predictive of a poorer prognosis (49).
		HNSCC	Tumor tissues	IL-10	B10 Breg with the CD24^hiCD38^hi and CD25^hi phenotypes have been found in the TME. CD24^hiCD38^hi B10 Breg have a higher expression of IL-10 than CD25^hi B10 Breg (44).
		HNSCC	Tumor-draining LNs	—	Breg cells correlate with non-metastatic LNs and low grade (50).
		Gastric cancer	Tumor tissues, PBMCs	IL-10, TGF-β	Inhibit the IFN-γ and TNF-α production of CD4⁺ T cells via IL-10; induce Treg cell proliferation via TGF-β (51).
		Multiple myeloma	Bone marrow, PBMCs	IL-10	Abrogate NK cell-mediated ADCC against multiple myeloma cells (52).
	CD19⁺CD24^hiCD27⁺	Pancreatic cancer	PBMCs	IL-10	CD19⁺CD24^hiCD27⁺ B10 Breg only produce IL-10, whereas CD19⁺CD24^hiCD38^hi immature B cells defined in the same study produce both IL-10 and IL-35 (53).
		Esophageal squamous cell carcinoma	PBMCs	IL-10	Tumor exosomes promote B10 Breg proliferation (54).
		Gastric cancer	Tumor tissues, PBMCs	—	Inhibit the proliferation and production of IFN-γ by CD4⁺ T cells (55).
	CD19⁺CD27⁺CD10^-	Gastric cancer	Tumor tissues, PBMCs	IL-10	Inhibit the production of IFN-γ, TNF, and IL-17 by CD4⁺ T cells; inhibit the production of IFN-γ and TNF by CD8⁺ T cells; stimulate IL-10 production by T cells (56).
	CD19⁺CD5⁺CD1d⁺	Cervical cancer, cervical intraepithelial neoplasia	PBMCs	IL-10	Inhibit the production of perforin and GrB by CD8⁺ T cells (57).
	CD19⁺CD5⁺CD1d⁺	HNSCC	Tumor-draining LNs	—	Good prognostic factor in TDLNs (50).
	CD19⁺CD5⁺	oesophageal cancer	PBMCs	IL-10	(58)
	CD19⁺CD5⁺	HNSCC	Tumor-draining LNs	—	Good prognostic factor in TDLNs (50).
	CD19⁺CD20⁺	Ovarian cancer	Ascites	IL-10	Inhibit the IFN-γ production of CD8⁺ T cells via IL-10 and decreased CD80/CD86 surface expression; negatively correlate with CD4⁺FoxP3⁺ Treg cells (59).
	CD19⁺	HNSCC	Tumor tissues, LNs	IL-10	Induce resting CD4⁺ T cells to differentiate into CD4⁺FoxP3⁺ Treg cells (21).
IL-35⁺ Breg	CD19⁺CD24^hiCD38^hi	Pancreatic cancer	PBMCs	IL-10, IL-35	Cause CD8⁺ T cell malfunction via IL-35/gp130/STAT3 signaling pathway (53).
IL-35⁺ Breg	CD20⁺	Pancreatic cancer	Tumor tissues	IL-35	Cause Treg cell expansion and CD4⁺ T cell suppression via IL-35 (60).
GrB⁺ Breg	CD19⁺CD38⁺CD1d^hiIgM⁺CD147⁺	Breast, ovarian, cervical, colorectal, and prostate cancers	Tumor tissues	GrB, IL-10, IL-12	GrB⁺ Breg cells inhibit T cell proliferation and receptor degradation (57, 61).
TIM-1⁺ Breg	CD5^hiCD27^-/+CD38^+/hiTIM-1⁺	Hepatocellular carcinoma	Tumor tissues, PBMCs	IL-10	Inhibit CD8⁺ T cell proliferation, and the production of TNF-α and IFN-γ (38).
PD-1⁺ Breg	CD5^hiCD27^hi/+CD38^dimPD-1⁺	Hepatocellular carcinoma	Tumor tissues, PBMCs	IL-10	Cause T cell exhaustion via the PD-L1-PD-1 axis (62).
PD-L1⁺ Breg	CD20⁺CD27^-PD-L1⁺	Melanoma	PBMCs	IgM, IgD	Inhibit the production of IFN-γ by T cells; express high IgM and IgD; linked to advanced tumor stages and metastasis (63).
ADO⁺ Breg	CD39⁺CD73⁺	HNSCC	Tumor tissues, PBMCs	ADO	Suppress the intracellular BTK and Ca²⁺ influx in effector B cells (22).
Plasmablast	CD19^lowCD27^hi	Colorectal cancer	Tumor tissues	—	Gut-homing, inhibit the production of IFN-γ and TNF-α by T cells, do not promote FoxP3 expression (64).
Plasmablast	CD138⁺IgA⁺PD-L1^-IL-10⁺	Prostate cancer	Tumor tissues	IL-10, TGF-β, IgA	Suppress cytotoxic CD8⁺ T cells (65).

HNSCC, head and neck squamous cell carcinoma; TME, tumor microenvironment; PBMC, peripheral blood mononuclear cells; LN, lymph node; B10 Breg, IL-10 producing regulatory B cell; T2-MZP, transitional 2-marginal zone precursor; GrB, granzyme B; ADO, adenosine; BTK, Bruton’s tyrosine kinase; ADCC, antibody-dependent cellular cytotoxicity; hi, high; dim, medium.