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.

Bladder cancer (BC) constitutes one of the most diagnosed types of cancer worldwide. Advancements in and new methodologies for DNA sequencing, leading to high-throughput microbiota testing, have pinpointed discrepancies in urinary microbial fingerprints between healthy individuals and patients with BC. Although several studies suggest an involvement of microbiota dysbiosis in the pathogenesis, progression, and therapeutic response to bladder cancer, an established direct causal relationship remains to be elucidated due to the lack of standardized methodologies associated with such studies. This review compiles an overview of the microbiota of the human urinary tract in healthy and diseased individuals and discusses the evidence to date on microbiome involvement and potential mechanisms by which the microbiota may contribute to the development of BC. We also explore the potential profiling of urinary microbiota as a biomarker for risk stratification, as well as the prediction of the response to intravesical therapies and immunotherapy in BC patients. Further investigation into the urinary microbiome of BC patients is imperative to unravel the complexities of the role played by host–microbe interactions in shaping wellness or disease and yield valuable insights into and strategies for the prevention and personalized treatment of BC.

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.

Graves’ disease (GD) is an autoimmune disorder, driven by the appearance of circulating autoantibodies (Ab) against the thyroid stimulating hormone (TSH) receptor, thus causing hyperthyroidism. While antithyroid drugs, the only available treatment for GD, carry a significant risk of relapse, advances in immunology could pave the way for more effective therapies. Natural killer (NK) cells, divided into cytotoxic CD56^dim and cytokine-secreting CD56^bright subsets, regulate immune responses through cytokine production and cell lysis and may play a role in the pathogenesis of GD. To investigate their involvement, we conducted flow cytometry on peripheral blood samples from 131 GD patients at various stages (disease onset, on antithyroid drugs, and in remission) and 97 age- and sex-matched healthy controls (HC). We analyzed NK cell subsets, activating (CD16, CD69, NKG2D, NKp30) and inhibitory receptors (CD161, NKG2A), degranulation (CD107a), and intracellular cytokines expression (interferon γ, tumor necrosis factor α). Statistical comparisons were made between GD patients and HC and across disease stages. GD patients had a higher frequency of total NK cells (p < 0.028) and CD56^bright NK cells (p < 0.01) but a lower frequency of CD56^dim NK cells (p = 0.005) compared to HC. NK cells in GD patients expressed activating receptors more frequently, except for NKG2D, but had decreased cytokine expression and degranulation ability. At GD onset, patients had higher frequencies of total NK cells, CD56^bright NK cells, and NK cells expressing activating receptors compared to patients receiving ATD treatment and those in remission. CD161⁺ NK cells were lower at GD onset and returned to levels of HC following treatment. Correlation analysis revealed that free thyroxine (FT4) levels were inversely correlated with CD107a⁺ NK cells (p < 0.05) and positively correlated with CD69⁺ NK cells (p < 0.01). These findings suggest that hyperthyroidism impairs NK cell degranulation, with the increased frequency of NK cells potentially compensating for their reduced function. This dysfunction may contribute to the unregulated immune response in GD, highlighting NK cells as a potential target for novel therapeutic strategies.

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 carcinoma but are limited by severe side effects. Innovative IL-2-based immunotherapeutic approaches include immunotoxins, such as antibody-drug conjugates, and immunocytokines, 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.