Dysregulation of the type 17 immune pathway has already been considered in schizophrenia and we previously measured decreased sera values of interleukin (IL)-17 in early stages. We further explored the possible correlation of IL-17 systemic levels with proinflammatory cytokines and cognitive scores and additionally analyzed the percentage of IL-17 producing lymphocytes in peripheral blood of patients with stable schizophrenia. We included 27 patients diagnosed with schizophrenia (F20), after a three-month stable depot antipsychotic therapy (risperidone or paliperidone) and 18 healthy control subjects. Positive and Negative Syndrome Scale of Schizophrenia and the Montreal-Cognitive Assessment (MoCA) were conducted. Sera concentrations of IL-17, IL-6, tumor necrosis factor alpha (TNF-α) and soluble ST2 receptor (sST2) were measured. Flow cytometry and Natural Killer (NK) and T cell analyses were done in 10 patients and 10 healthy controls. Moderate positive correlation was established between IL-17 and TNF-α (r = 0.640; p = 0.001), IL-17 and IL-6 (r = 0.514; p = 0.006), IL-17 and sST2 (r = 0.394; p = 0.042). Furthermore, a positive correlation between the serum levels of IL-17 and MoCA scores was observed, especially with visuospatial and executive functioning, as well as language functioning and delayed recall (p < 0.05). Significantly higher percentage of IL-17 producing CD56⁺ NK cells was measured in peripheral blood of patients with schizophrenia in remission vs. healthy individuals (p = 0.001). The percentage of CD4⁺ T cells and CD4⁺ T cells that produce IL-17 was significantly increased in patients (p = 0.001). This study revealed the involvement of innate type 17 immune response in the progression of inflammation and this could be related to cognitive functioning in stable schizophrenia.

Semaglutide, a glucagon-like peptide 1 receptor agonist, is an antidiabetic that has recently shown promising immunomodulatory and antitumor effects. Breast cancer is the most common type of cancer affecting women worldwide. The aim of this study was to analyze the effects of semaglutide on the antitumor immunity in a 4T1 mouse breast cancer model. After induction of breast cancer, BALB/C mice were treated intraperitoneally with semaglutide. Semaglutide administration decelerated tumor appearance, growth and progression. The antidiabetic drug showed neither a direct cytotoxic effect in vitro, nor an angiogenic effect. Furthermore, depletion of NK cells had no affect on tumor growth in semaglutide treated mice suggesting a non-NK cell-dependent mechanism. However, semaglutide increased the accumulation and maturation of CD11c⁺ dendritic cell, while decreasing the percentage of FoxP3⁺ regulatory T cells in the spleen and primary tumor. In addition, semaglutide increased tumor infiltration and promoted the antitumor phenotype of T cells, in vivo. Furthermore, semaglutide enhanced the cytotoxic capacity of CD8⁺ T cells, in vitro. These results suggest that semaglutide enhances the acquired antitumor immune response and has potential for the future treatment of malignancies.

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.

Interleukin-33 (IL-33) has emerged as a critical cytokine in the regulation of the immune system, showing a pivotal role in the pathogenesis of various diseases including cancer. This review emphasizes the role of the IL-33/ST2 axis in breast cancer biology, its contribution to cancer progression and metastasis, its influence on the tumor microenvironment and cancer metabolism, and its potential as a therapeutic target. The IL-33/ST2 axis has been shown to have extensive pro-tumorigenic features in breast cancer, starting from tumor tissue proliferation and differentiation to modulating both cancer cells and anti-tumor immune response. It has also been linked to the resistance of cancer cells to conventional therapeutics. However, the role of IL-33 in cancer therapy remains controversial due to the conflicting effects of IL-33 in tumorigenesis and anti-tumor response. The possibility of targeting the IL-33/ST2 axis in tumor immunotherapy, or as an adjuvant in immune checkpoint blockade therapy, is discussed.

The organic ester O,O'-diethyl-(S,S)-ethylenediamine-N,N'-di-2-(3-cyclohexyl)propanoate dihydrochloride attenuates murine breast cancer growth and metastasis The organic ester O,O'-diethyl-(S,S)-ethylenediamine-N,N'-di-2-(3-cyclohexyl)propanoate dihydrochloride attenuates murine breast cancer growth and metastasis

Background/Objectives: In recent years, silver complexes have shown strong antibacterial, antifungal, and antitumor activity with high selectivity toward cancer cells. Their cytotoxic effects are mainly linked to apoptosis induction, DNA damage, and enzyme inhibition, while the antitumor activity of silver(I) complexes with S-alkyl thiosalicylic acid derivatives remains unexplored. Methods: Silver(I) complexes with S-alkyl derivatives of thiosalicylic acid (C1–C5) were obtained through the direct reaction of silver(I) nitrate, the corresponding ligand of thiosalicylic acid, and a sodium hydroxide solution. The interactions between the complexes and CT-DNA/BSA were studied using UV-Vis, fluorescence spectroscopy, and molecular docking studies. The cytotoxic capacity of the newly synthesized complexes was assessed by an MTT assay. Results: Complexes C1–C5 exhibited strong cytotoxicity against murine and human breast (4T1, MDA-MB-468), colon (CT26, HCT116), and lung (LLC1, A549) cancer cell lines. The C3 complex significantly diminished tumor progression in an orthotropic mammary carcinoma model while demonstrating good systemic tolerance. Conclusions: The tested complex C3 triggered apoptosis in 4T1 cells by altering the delicate balance between pro- and anti-apoptotic Bcl-2 family members, increasing reactive oxygen species (ROS) levels, and reducing mitochondrial membrane depolarization. Moreover, the C3 arrested the 4T1 cell cycle in G0/G1 phase, decreasing the expression of cyclin D3 and increasing the expression of p16, p21, and p27.