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Harnessing Metformin's Immunomodulatory Effects on Immune Cells to Combat Breast Cancer
Metformin, a medication known for its anti-glycemic properties, also demonstrates potent immune system activation. In our study, using a 4T1 breast cancer model in BALB/C WT mice, we examined metformin's impact on the functional phenotype of multiple immune cells, with a specific emphasis on na...
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Published in: | International journal of molecular sciences 2024-06, Vol.25 (11), p.5869 |
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Main Authors: | , , , , , , , , , , |
Format: | Article |
Language: | English |
Subjects: | |
Citations: | Items that this one cites |
Online Access: | Get full text |
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Summary: | Metformin, a medication known for its anti-glycemic properties, also demonstrates potent immune system activation. In our study, using a 4T1 breast cancer model in BALB/C WT mice, we examined metformin's impact on the functional phenotype of multiple immune cells, with a specific emphasis on natural killer T (NKT) cells due to their understudied role in this context. Metformin administration delayed the appearance and growth of carcinoma. Furthermore, metformin increased the percentage of IFN-γ
NKT cells, and enhanced CD107a expression, as measured by MFI, while decreasing PD-1
, FoxP3
, and IL-10
NKT cells in spleens of metformin-treated mice. In primary tumors, metformin increased the percentage of NKp46
NKT cells and increased FasL expression, while lowering the percentages of FoxP3
, PD-1
, and IL-10-producing NKT cells and KLRG1 expression. Activation markers increased, and immunosuppressive markers declined in T cells from both the spleen and tumors. Furthermore, metformin decreased IL-10
and FoxP3
Tregs, along with Gr-1
myeloid-derived suppressor cells (MDSCs) in spleens, and in tumor tissue, it decreased IL-10
and FoxP3
Tregs, Gr-1
, NF-κB
, and iNOS
MDSCs, and iNOS
dendritic cells (DCs), while increasing the DCs quantity. Additionally, increased expression levels of MIP1a, STAT4, and NFAT in splenocytes were found. These comprehensive findings illustrate metformin's broad immunomodulatory impact across a variety of immune cells, including stimulating NKT cells and T cells, while inhibiting Tregs and MDSCs. This dynamic modulation may potentiate its use in cancer immunotherapy, highlighting its potential to modulate the tumor microenvironment across a spectrum of immune cell types. |
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ISSN: | 1422-0067 1661-6596 1422-0067 |
DOI: | 10.3390/ijms25115869 |