B cell regulation of the anti-tumor response and role in carcinogenesis

Schwartz, Marc; Zhang, Yu; Rosenblatt, Joseph D.

doi:10.1186/s40425-016-0145-x

Table 1 Breg markers of immune suppression and tumorigenesis

From: B cell regulation of the anti-tumor response and role in carcinogenesis

Breg marker	Mechanisms	Phenotype(s)	Cancer type(s)	References
IL-10	↓Th1/Th17; ↑Treg generation	Human:	HNSCC, lung, esophageal, ovarian, glioma, gastric	[5, 13–22, 25, 37, 38, 44, 56, 65]
		CD19⁺CD24^hiCD38^hi
		CD19⁺CD1d^hiCD5⁺
		CD19⁺CD24^hiCD27⁺
		CD19⁺CD25^hi
		Mouse:
		CD19⁺CD1d^hiCD5⁺
		CD19 + CD25 + B220+
Granzyme-B	↓T cell proliferation via degradation of TCR-zeta chain	Human:	Breast, ovarian, cervical, colorectal, prostate	[62]
Granzyme-B	↓T cell proliferation via degradation of TCR-zeta chain	CD19 + CD38 + CD1d + IgM + CD147+	Breast, ovarian, cervical, colorectal, prostate	[62]
IL-35	↓Th1/Th17; ↑Treg generation	Human:	Pancreatic	[76–79]
		CD19 + CD35+
		Mouse:
		CD19⁺CD1d^hiCD5⁺
TGFβ	↑Treg generation	Human:	Multiple tumor types	[5, 20, 44, 65]
		CD19⁺CD24^hiCD38^hi
		Mouse:
		CD19⁺CD25⁺B220⁺
Stat3	↑Treg generation; ↑angiogenesis	Human:	Melanoma, gastric, lung, liver, prostate	[57, 73–75]
		CD5+
		Mouse:
	↑IL-10, ↑TGFβ	CD19⁺CD25⁺B220⁺
Lymphotoxin-α/β	Activation of IKKα and STAT3	Mouse:	Castration-resistant prostate (mice)	[93]
Lymphotoxin-α/β	Activation of IKKα and STAT3	CD19 + LT+	Castration-resistant prostate (mice)	[93]
PD-L1	Promote T cell anergy via interaction with PD1	Human:	B cell lymphomas, prostate	[26–28, 69, 88]
		Malignant B cells
		IgA + CD138+
		Mouse:
		IgA + CD138+
PD-1	Promote T cell anergy	Human:	Hepatocellular	[15]
PD-1	Promote T cell anergy	CD19 + CD5^hiCD24^−/+CD27^hi/+CD38^dim	Hepatocellular	[15]
TNFα	↑IL-10+ Bregs, ↓CD8 + IFNγ Tcells	Mouse:	Squamous cell skin CA (mice)	[90]
TNFα	↑IL-10+ Bregs, ↓CD8 + IFNγ Tcells	CD19 + TNFα+	Squamous cell skin CA (mice)	[90]
OX40L	↑Th2 skewing, ↓CD8 + IFNγ Tcells	Mouse:	Colorectal (mice)	[64]
OX40L	↑Th2 skewing, ↓CD8 + IFNγ Tcells	CD19 + OX40L+	Colorectal (mice)	[64]
CD80, CD86	↓T cell proliferation via interaction with CTLA-4; may also ↑T cell proliferation via interaction with CD28	Human	Multiple tumor types	[30, 44, 69]
CD80, CD86		CD19⁺CD24^hiCD38^hi	Multiple tumor types	[30, 44, 69]
IL-8	Upregulation of androgen receptor and downstream MMPs	Human:	Bladder	[22]
IL-8	Upregulation of androgen receptor and downstream MMPs	CD19 + IL-8+	Bladder	[22]
FasL	Induce T cell apoptosis via binding to Fas	Human:	CLL	[60, 61]
FasL	Induce T cell apoptosis via binding to Fas	Malignant B cells	CLL	[60, 61]
CD40L	Interact with CD40 on malignant cells to stimulate ↑IL-10, ↑TGFβ	Human:	Hepatocellular	[19]
CD40L		CD19⁺CD24^hiCD38^hi	Hepatocellular	[19]
CD5	Activation of Stat3 via binding to IL-6	Human:	Lung, prostate	[57]
CD5	Activation of Stat3 via binding to IL-6	CD19⁺CD5⁺IL-10+	Lung, prostate	[57]
BTK	Repolarization of macrophages toward M2-type	Mouse:	Pancreatic (mice)	[82]
BTK	Repolarization of macrophages toward M2-type	CD19 + BTK+	Pancreatic (mice)	[82]

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