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Published on: June 9, 2023
IL-25 blockade inhibits metastasis in breast cancer
Zhujun Jiang1, Jingtao Chen2, Xuemei Du3
1Institute for Immunology and School of Medicine, Tsinghua University, Beijing, 100084, China.
Abstract:
Metastasis is the leading cause of death in breast cancer patients. However, the mechanisms underlying metastasis are not well understood and there is no effective treatment in the clinic. Here, we demonstrate that in MMTV-PyMT, a highly malignant spontaneous breast tumor model, IL-25 (also called IL-17E) was expressed by tumor-infiltrating CD4+ T cells and macrophages. An IL-25 neutralization antibody, while not affecting primary tumor growth, substantially reduced lung metastasis. Inhibition of IL-25 resulted in decreased type 2 T cells and macrophages in the primary tumor microenvironments, both reported to enhance breast tumor invasion and subsequent metastasis to the lung. Taken together, our data suggest IL-25 blockade as a novel treatment for metastatic breast tumor.
Insights
Interleukin-25 (IL-25) blockade significantly reduced breast cancer lung metastasis in a mouse model. This approach targets tumor-infiltrating immune cells, offering a potential new treatment for metastatic breast cancer.
Area of Science:
- Oncology
- Immunology
- Cancer Research
Background:
- Metastasis is the primary cause of mortality in breast cancer patients.
- The underlying mechanisms of metastasis are not fully understood, limiting effective clinical treatments.
Purpose of the Study:
- To investigate the role of Interleukin-25 (IL-25) in breast cancer metastasis.
- To evaluate the therapeutic potential of IL-25 blockade in a preclinical breast cancer model.
Main Methods:
- Utilized the MMTV-PyMT spontaneous breast tumor mouse model.
- Administered an IL-25 neutralization antibody to assess its impact on metastasis.
- Analyzed changes in tumor-infiltrating CD4+ T cells and macrophages.
Main Results:
- IL-25 was expressed by tumor-infiltrating CD4+ T cells and macrophages.
- IL-25 blockade did not affect primary tumor growth but substantially reduced lung metastasis.
- Inhibition of IL-25 led to decreased type 2 T cells and macrophages in the tumor microenvironment.
Conclusions:
- IL-25 blockade represents a promising novel therapeutic strategy for metastatic breast cancer.
- Targeting IL-25 may disrupt the tumor microenvironment, inhibiting invasion and metastasis.
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