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Effective cancer therapies must address the tumor microenvironment (TME), a complex network of tumor cells and stromal components, including endothelial, immune, and mesenchymal cells. Durable outcomes require targeting both tumor cells and the TME while minimizing systemic toxicity. Interleukin-2 (IL-2)-based therapies have shown efficacy in cancers such as metastatic melanoma and renal cell carcinoma but are limited by severe side effects. Innovative IL-2-based immunotherapeutic approaches include immunotoxins, such as antibody–drug conjugates, immunocytokines, and antibody–cytokine fusion proteins that enhance tumor-specific delivery. These strategies activate cytotoxic CD8+ T lymphocytes and natural killer (NK) cells, eliciting a potent Th1-mediated anti-tumor response. Modified IL-2 variants with reduced Treg cell activity further improve specificity and reduce immunosuppression. Additionally, IL-2 conjugates with peptides or anti-angiogenic agents offer improved therapeutic profiles. Combining IL-2-based therapies with immune checkpoint inhibitors (ICIs), anti-angiogenic agents, or radiotherapy has demonstrated synergistic potential. Preclinical and clinical studies highlight reduced toxicity and enhanced anti-tumor efficacy, overcoming TME-driven immune suppression. These approaches mitigate the limitations of high-dose soluble IL-2 therapy, promoting immune activation and minimizing adverse effects. This review critically explores advances in IL-2-based therapies, focusing on immunotoxins, immunocytokines, and IL-2 derivatives. Emphasis is placed on their role in combination strategies, showcasing their potential to target the TME and improve clinical outcomes effectively. Also, the use of IL-2 immunocytokines in "in situ" vaccination to relieve the immunosuppression of the TME is discussed. [ABSTRACT FROM AUTHOR]

The gut microbiota, a diverse collection of microorganisms in the gastrointestinal tract, plays a critical role in regulating metabolic, immune, and cognitive functions. Disruptions in the composition of these microbial communities, termed dysbiosis, have been linked to various neurodegenerative diseases (NDs), such as Parkinson's disease (PD) and Alzheimer's disease (AD). One of the key pathological features of NDs is neuroinflammation, which involves the activation of microglia and peripheral immune cells. The gut microbiota modulates immune responses through the production of metabolites and interactions with immune cells, influencing the inflammatory processes within the central nervous system. This review explores the impact of gut dysbiosis on neuroinflammation, focusing on the roles of microglia, immune cells, and potential therapeutic strategies targeting the gut microbiota to alleviate neuroinflammatory processes in NDs. [ABSTRACT FROM AUTHOR]

In recent years, many attempts have been made to find novel anticancer agents for the treatment of advanced and metastatic gastric cancers. Metal nanoparticles (NPs) have gained attention for their unique characteristics to be used in anticancer chemotherapy. Silver and platinum have been extensively studied for their biomedical applications. However, the functionalization of such NPs was less described. In this work, we synthesized PtFe2O4 NPs and conjugated them with silver NPs using the Scenedesmus obliquus extract. The synthesized nanocomposite was characterized using physiochemical assays and then, cytotoxicity potential of PtFe2O4@Ag nanocomposite against AGS cells was investigated. Proper synthesis of PtFe2O4@Ag NPs was confirmed by the XRD, SEM and TEM, and FT-IR. The spherical nanocomposite was synthesized with a size range of 20–40 nm. Also, the purity of the nanocomposite was evaluated using EDX assay, and the stability of the particles was determined by zeta potential (− 35.2 mV). The AGS cells were more susceptible to the nanocomposite (IC50 = 48 µg/mL) than HEK293 cells (IC50 = 158 µg/mL). Hoechst staining and flow cytometry assay indicated nuclear damages, chromatin fragmentation, and also apoptosis induction among nanocomposite treated cells. Following exposure to PtFe2O4@Ag NPs, the expression and activity of caspase-3 were reduced by 1.41 and 1.9 folds, respectively. The qRT-PCR assay showed that the expression of the Bax gene increased by 2.2 folds and the Bcl2 gene reduced to 0.62 folds, in comparison with the control cells. This work showed a promising anticancer potential of PtFe2O4@Ag NPs towards gastric cancer cells and elucidated the molecular mechanism of their cytotoxicity potential via triggering the apoptotic pathway. [ABSTRACT FROM AUTHOR]