Changes in the composition of immune cells in the tumor microenvironment of MMTV-PyMT breast cancer mice at different ages
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1. School of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou 310053, China; 2. Second Clinical Hospital of Zhejiang Chinese Medical University, Hangzhou 310053, China; 3. Jinhua Academy of Zhejiang Chinese Medical University, Hangzhou 310053, China

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    Abstract:

    Objective This study aimed to investigate the tumorigenic properties of MMTV-PyMT breast cancer transgenic mice at different ages (in weeks) and the changes in the composition of immune cells in the tumor microenvironment. Methods Eight groups of 4, 6, 8, 10, 12, 14, 16 and 18 weeks of age MMTV-PyMT female mice (FVB mice as the background) and one group of 8 weeks of FVB female mice were prepared for routine blood testing, the pathological changes of the mammary gland and lung metastases were observed by histopathological sections, and the immune cells in blood, spleen, and tumor were analyzed by flow cytometry. Results MMTV-PyMT mice showed adenular ductal lesions at 4 ~ 6 weeks of age; the ductal portion expanded to the growth boundary at 8 ~ 9 weeks of age, and then gradually broke through the glandular boundary to form early breast cancer at 8 ~ 12 weeks of age, and advanced breast cancer at 10 ~ 14 weeks of age. At 12 weeks of age, metastases were visible in the lungs of some mice, and at 14 weeks of age, the number of metastases in the lungs increased significantly. As the age of the mice increased, the number of white blood cells, neutrophils, and platelets in their blood increased gradually, while the lymphocytes and erythrocytes showed a gradual downward trend. Flow cytometry showed that with the increase in age, the proportion of T cells in the spleen and tumor gradually decreased, the MDSCs in the blood, spleen, and tumor gradually increased, and the NK cells in the tumor also gradually increased. Conclusions This study analyzed routine blood tests, pathology, and immune cells in the tissues of MMTV-PyMT mouse models of different weeks of age, providing a novel perspective on the dynamic alterations of the tumor immune microenvironment during the malignant progression of breast cancer.

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History
  • Received:August 08,2024
  • Revised:
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  • Online: September 01,2025
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