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Journal of Translational Medicine
Published in: Journal of Translational Medicine 1/2022

Open Access 01-12-2022 | Breast Cancer | Research

Pharmaceutical targeting Th2-mediated immunity enhances immunotherapy response in breast cancer

Authors: Yuru Chen, Jiazheng Sun, Yachan Luo, Jiazhou Liu, Xiaoyu Wang, Rui Feng, Jing Huang, Huimin Du, Qin Li, Jinxiang Tan, Guosheng Ren, Xiaoyi Wang, Hongzhong Li

Published in: Journal of Translational Medicine | Issue 1/2022

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Abstract

Background

Breast cancer is a complex disease with a highly immunosuppressive tumor microenvironment, and has limited clinical response to immune checkpoint blockade (ICB) therapy. T-helper 2 (Th2) cells, an important component of the tumor microenvironment (TME), play an essential role in regulation of tumor immunity. However, the deep relationship between Th2-mediated immunity and immune evasion in breast cancer remains enigmatic.

Methods

Here, we first used bioinformatics analysis to explore the correlation between Th2 infiltration and immune landscape in breast cancer. Suplatast tosilate (IPD-1151 T, IPD), an inhibitor of Th2 function, was then employed to investigate the biological effects of Th2 blockade on tumor growth and immune microenvironment in immunocompetent murine breast cancer models. The tumor microenvironment was analyzed by flow cytometry, mass cytometry, and immunofluorescence staining. Furthermore, we examined the efficacy of IPD combination with ICB treatment by evaluating TME, tumor growth and mice survival.

Results

Our bioinformatics analysis suggested that higher infiltration of Th2 cells indicates a tumor immunosuppressive microenvironment in breast cancer. In three murine breast cancer models (EO771, 4T1 and EMT6), IPD significantly inhibited the IL-4 secretion by Th2 cells, promoted Th2 to Th1 switching, remodeled the immune landscape and inhibited tumor growth. Remarkably, CD8+ T cell infiltration and the cytotoxic activity of cytotoxic T lymphocyte (CTL) in tumor tissues were evidently enhanced after IPD treatment. Furthermore, increased effector CD4+ T cells and decreased myeloid-derived suppressor cells and M2-like macrophages were also demonstrated in IPD-treated tumors. Importantly, we found IPD reinforced the therapeutic response of ICB without increasing potential adverse effects.

Conclusions

Our findings demonstrate that pharmaceutical inhibition of Th2 cell function improves ICB response via remodeling immune landscape of TME, which illustrates a promising combinatorial immunotherapy.
Appendix
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Metadata
Title
Pharmaceutical targeting Th2-mediated immunity enhances immunotherapy response in breast cancer
Authors
Yuru Chen
Jiazheng Sun
Yachan Luo
Jiazhou Liu
Xiaoyu Wang
Rui Feng
Jing Huang
Huimin Du
Qin Li
Jinxiang Tan
Guosheng Ren
Xiaoyi Wang
Hongzhong Li
Publication date
01-12-2022
Publisher
BioMed Central
Published in
Journal of Translational Medicine / Issue 1/2022
Electronic ISSN: 1479-5876
DOI
https://doi.org/10.1186/s12967-022-03807-8

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WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

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