Abstract
The balance between immune effector cells such as T cells and natural killer cells, and immunosuppressive Treg cells, dendritic, myeloid and monocytic sub-populations in the tumor microenvironment acts to calibrate...
Highlights
A subset of B cells identified as B-regulatory cells (Bregs) have recently emerged as major contributors to the pathogenesis of autoimmune and neoplastic disorders
GrB+ Bregs and adjacent IL-21-producing T cells were found in the microenvironment of several human tumors including breast, ovarian, cervical, colorectal, and prostate tumors [62]. These findings suggest that IL-21-dependent GrB+ Bregs may attenuate local anti-tumor immune responses in a manner similar to Tregulatory cells (Tregs), by directly inhibiting the proliferation of CD4+ and CD8+ effector T cells
Administration of anti-CD40L antibody blocked hepatocellular cancer (HCC) tumor growth enhancement by Bregs in vivo, blocked enhancement of HCC cell proliferation by Bregs in vitro and decreased IL-10 and TGF-β1 secretion while promoting an increase of TNFα secretion. These results suggest that an expanded CD19+CD24+CD38+ peripheral blood Breg population in patients with HCC may migrate to the tumor margin and mediate tumor growth via local elaboration of immunosuppressive cytokines IL-10 and TGF-β, dependent on cognate interactions between CD40L and CD40 on Bregs and HCC cells respectively
Summary
A subset of B cells identified as B-regulatory cells (Bregs) have recently emerged as major contributors to the pathogenesis of autoimmune and neoplastic disorders. Treatment with CpGODN reversed the reduced expression of 4-1BBL on murine and human Bregs in vitro as well as in vivo in tumor-bearing mice, resulting in emergence of a CD20high41BBLhigh B cell subset.
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