Regulatory B Cells: Key Players in Hepatocellular Carcinoma Progression

Abstract

Hepatocellular carcinoma HCC represents a major health problem and ranked as the sixth most common cancer worldwide and the third most common cause of cancer related mortality The prognosis of HCC is usually poor due to post surgery recurrence and metastasis Both Cells mediated and humoral immunity is considered as key players in the immunopathology of HCC Recently there is a special subset of B cells defined as regulatory B cells Bregs found to be abundant in the tumor microenvironment and was a leading cause of progression of various cancers including HCC nbsp Bregs arise from a common progenitor named transitional marginal zone precursor T MZP B cells as they have most of the indicated markers for Bregs Human Bregs or also known as human IL producing B cells B is a subset of B cells is enriched in the CD CD highCD minus CD highCD dhighCD transitional B cell subset Tumor Evoked Regulatory B Cells tBreg exert antitumor activity by promoting conversion of the resting CD T cell into FoxP Treg by secretion of TGF beta then the Treg inhibit T cell proliferation and promote tumor metastasis by suppression of the anti tumor effects of CD T cells and NK cells nbsp Bregs may suppress the antitumor immunity and promote HCC progression via several mechanisms including the CD CD L signaling mediated cytokine production of IL TGF beta which down regulate TNF alpha PD hi B cell Granzyme B secreting B cells GrB B cells Treg upregulation TH downregulation and IL which triggers the genesis of Tregs from naive T cells with subsequent suppression of the anticancer immune response The hallmark of Breg function is IL which inhibits proin ammatory cytokines and supports Treg differentiation In this review we highlight the role and mechanisms by which Breg cells are involved in HCC Understanding these mechanisms may direct us to a novel therapeutic approach targeting Breg for treatment of HCC