Deciphering interleukin 10’s dual role: insights into B cell dynamics in breast tumor-draining lymph nodes
1
Department of Immunology and Allergy, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
2
Shiraz Institute for Cancer Research, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
3
Department of Pathology, Shiraz Central Hospital, Shiraz, Iran
4
Breast Diseases Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
5
Immunology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
6
Department of Immunology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
Submission date: 2025-02-04
Final revision date: 2025-05-07
Acceptance date: 2025-08-05
Online publication date: 2026-07-20
Corresponding author
Fereshteh Mehdipour
Shiraz Institute for Cancer Research, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
Shiraz Institute for Cancer Research, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
KEYWORDS
ABSTRACT
The immune-modulatory role of interleukin 10 (IL-10) in breast cancer remains controversial, with reports of both pro- and anti-tumor effects. While B cells are important targets of IL-10, the frequency, phenotype, and functional impact of B cells expressing IL-10 receptor (IL-10R) in tumor-draining lymph nodes (TDLNs) of breast cancer patients are still unclear. In this study, we analyzed axillary lymph nodes from 49 breast cancer patients, assessing IL-10R expression on B cells and the effects of recombinant IL-10 (rIL-10) on granzyme B, CD86, and tumor necrosis factor (TNF-) production. Flow cytometry revealed that 52.9 ±17.3% of B cells expressed IL-10R, predominantly exhibiting an activated/memory phenotype (CD27+CD24hi). Interestingly, IL-10R+ B cells were significantly reduced in metastatic lymph nodes (MLNs) compared to non-metastatic lymph nodes (nMLNs), suggesting a protective role in early disease. Paradoxically, HER2+ tumors exhibited higher frequencies of IL-10R+ B cells, indicating context-dependent functions. Functional assays demonstrated that IL-10 significantly enhanced granzyme B production in B cells but suppressed TNF-hi B cells by approximately 40%, without altering CD86 expression. These findings highlight the dual role of IL-10 in modulating B cell-mediated immunity. IL-10 enhances cytotoxic function via granzyme B while dampening antitumor TNF- responses. The reduced frequency of IL-10R+ B cells in MLNs suggests their potential role in anti-tumor immunity, while their association with HER2+ tumors may indicate a pro-tumor function in certain contexts. This study emphasizes the complexity of IL-10 signaling in B-cell-mediated immunity, shedding light on its multifaceted effects and the need to clarify the role of IL-10 in cancer immunity.
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