Pro- and Anti- Effects of Immunoglobulin A- Producing B Cell in Tumors and Its Triggers.

Ziwen Zhong,Wenchang Zhou,Meilin Weng,Ronghua Liu,Zhiqiang Wang,Yiwei Chu,Ying Yue,Changhong Miao,Ke Nan

doi:10.3389/fimmu.2021.765044

Abstract

B cells are well known as key mediators of humoral immune responses via the production of antibodies. Immunoglobulin A (IgA) is the most abundantly produced antibody isotype and provides the first line of immune protection at mucosal surfaces. However, IgA has long been a divisive molecule with respect to tumor progression. IgA exerts anti- or pro-tumor effect in different tumor types. In this review, we summarize emerging evidence regarding the production and effects of IgA and IgA+ cells in the tumor microenvironment (TME). Moreover, we discuss that the TME cytokines, host diet, microbiome, and metabolites play a pivotal role in controlling the class-switch recombination (CSR) of IgA. The analysis of intratumoral Ig repertoires and determination of metabolites that influence CSR may help establish novel therapeutic targets for the treatment of cancers.

Highlights

Immunoglobulin A (IgA) is the most abundant antibody class present on mucosal surfaces
A high IgA proportion correlates with low clonality, resulting in a negative outcome [2]. These results can be explained by a focused immune response leading to the production of high-affinity, tumor-specific IgG1 antibodies; switching of B cells to the IgA isotype is not driven by particular antigens but is a passive consequence of the intratumoral suppressive cytokine environment [40]
May be driven by a focused immune response and may result in a better prognosis, whereas high IgA expression and low clonality mean that an immunosuppressive microenvironment drives IgA production and is likely to contribute to poor outcomes in some specific malignancies

Summary

INTRODUCTION

Immunoglobulin A (IgA) is the most abundant antibody class present on mucosal surfaces. IgA+ cells promote the expansion of Treg cell populations, whereas Treg cells produce TGF-b, which mediates the isotype class switch to IgA [9, 38] This regulatory loop induces a state of relative immune suppression and may further promote tumor progression in at least some cancer types or subtypes (Figure 2). Expressed on macrophages, natural killer (NK) cells and neutrophils, high levels of production of IgA block ADCC and ADCP [39, 40] Such antibodies can form immune complexes with tumor or non-tumor antigens, promoting chronic inflammation, tissue remodeling [41,42,43]. Monomeric IgA exerts inhibitory effects on many immune cell subsets by activating the myeloid-cell-specific type I

87 Transplanted tumor models TRAMP transgenic tumor models

Findings

CONCLUSION