# Regulatory B Cells in Tumor Microenvironment

**Authors:** Zhuoyan Cai, Lin Xie

PMC · DOI: 10.3390/cimb48010106 · 2026-01-20

## TL;DR

This review explores how regulatory B cells in the tumor microenvironment affect immune responses and cancer progression, and how targeting them could improve cancer treatments.

## Contribution

The paper introduces novel perspectives on Breg regulation through epigenetics and metabolism, and highlights new therapeutic strategies.

## Key findings

- Bregs use epigenetic and metabolic changes to regulate immune responses in the tumor microenvironment.
- STAT3 inhibitors like lipoxin A4 and resveratrol show potential in reducing Breg immunosuppressive activity.
- Targeting Bregs could enhance immunotherapy by preventing tumor immune escape.

## Abstract

Regulatory B cells (Bregs) are integral to the tumor microenvironment (TME) and influence immune responses through the secretion of immunosuppressive cytokines such as IL-10, IL-35, and TGF-β. This review highlights recent findings on the phenotype and mechanisms of Bregs, emphasizing their dual role in regulating immune responses within the TME. Importantly, we further explored the latest advances in Breg regulatory mechanisms from the novel perspectives of epigenetics and metabolic remodeling, including the effects of DNA methylation, histone acetylation, glycolysis, and oxidative phosphorylation on Bregs. We also investigate the therapeutic targeting of Bregs, with a focus on STAT3 inhibitors such as lipoxin A4, cucurbitacins, and resveratrol, which show promising potential in mitigating the suppressive function of Bregs. Furthermore, this review provides a detailed analysis of the impact of Bregs on tumorigenesis and metastasis, emphasizing the importance of inhibiting specific immune pathways to prevent tumor escape. Finally, this review offers a prospective outlook on immunotherapy strategies based on Bregs, foreseeing a more nuanced understanding of their TME function and the evolution of targeted treatments with enhanced therapeutic efficacy.

## Linked entities

- **Proteins:** IL10 (interleukin 10), TGFB1 (transforming growth factor beta 1), STAT3 (signal transducer and activator of transcription 3)
- **Chemicals:** lipoxin A4 (PubChem CID 3934), cucurbitacins (PubChem CID 119287), resveratrol (PubChem CID 5056)

## Full-text entities

- **Genes:** IL10 (interleukin 10) [NCBI Gene 3586] {aka CSIF, GVHDS, IL-10, IL10A, TGIF}, TGFB1 (transforming growth factor beta 1) [NCBI Gene 7040] {aka CAEND1, CED, DPD1, IBDIMDE, LAP, TGF-beta1}, STAT3 (signal transducer and activator of transcription 3) [NCBI Gene 6774] {aka ADMIO, ADMIO1, APRF, HIES}
- **Diseases:** Tumor (MESH:D009369), tumorigenesis (MESH:D063646), metastasis (MESH:D009362)
- **Chemicals:** cucurbitacins (MESH:D054728), lipoxin A4 (MESH:C040527), resveratrol (MESH:D000077185)

## Figures

1 figure with captions in the complete paper: https://tomesphere.com/paper/PMC12840374/full.md

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Source: https://tomesphere.com/paper/PMC12840374