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.

Metabolic syndrome (MetS) and ulcerative colitis (UC) are widespread health conditions characterized by chronic, low-grade inflammation. Galectin-1 (Gal-1), an immunomodulatory peptide mainly secreted from adipose tissue, could potentially play a crucial role in mitigating these conditions. This cross-sectional study explores the involvement of Gal-1 in MetS and UC within a cohort of 75 patients, newly diagnosed with UC. The MetS subgroup displayed increased fecal Gal-1 levels compared to those without MetS. Furthermore, Gal-1 showed predominance over pro-inflammatory cytokines, including TNF-α, IL-6, and IL-17, in these subjects. These findings emphasize the potential involvement of Gal-1 in the pathophysiology of UC and MetS, presenting it as a promising diagnostic biomarker and therapeutic target for these conditions.

In breast cancer therapy, as the leading cause of death in women, besides chemo-radiotherapy, immunotherapy has been increasingly used. PD-1/PD-L1 axis blockade primarily acts on T lymphocytes, the main effectors of acquired immune response. NK cells, which are part of the innate immune response, also play a role in the anti-tumor response through the blockade of this signaling pathway. The study was conducted to examine the effects of anti-PD-1 therapy on NK and T cells in mouse breast cancer. Female BALB/c mice were used, divided into two groups, one with induced breast cancer and one treated with anti-PD-1 antibody. Breast cancer cell line was used to induce the cancer, and the anti-PD-1 antibody was applied intraperitoneally. Cell populations in spleen and tumor microenvironment were examined using flow cytometry. Data were statistically analyzed using SPSS. The percentage of NK cells expressing FasL, NKG2D, and IFN-γ is significantly higher in spleen and tumor-infiltrating NK cells upon anti-PD-1 therapy, while the expression of inhibitory markers Foxp3 and IL-10 in regulatory NK cells is significantly lower. The percentage of T lymphocytes expressing CD107a and IL-17 is significantly higher in the spleen, while a higher number of T lymphocytes expressing CD69 is present in the