Immuno

The inflammatory and metabolic complexity of colitis necessitates therapies that act on multiple immune pathways. Using serum proteomic profiling, the present study evaluated the systemic immunomodulatory profile of Epilobium angustifolium lyophilized methanol-aqueous extract rich in oenothein B (EAE) in a dextran sulfate sodium (DSS)-induced mouse model of ulcerative colitis in a comparative manner to dexamethasone (DXM). DSS exposure triggered robust inflammatory activation, evidenced by elevated chemokines (CXCL9, CXCL10, CCL11), proinflammatory cytokines (IL-1α, IL-12, PAI-1, RAGE) and metabolic stress mediators (leptin, resistin, FGF-21). Treatment with EAE significantly attenuated this inflammatory profile, notably reducing Th2-skewed chemokines and eosinophil recruitment. In contrast to DXM, EAE uniquely normalized pro-thrombotic and tissue-remodeling markers, including PAI-1 and RAGE, both implicated in intestinal barrier dysfunction and chronic inflammation. Furthermore, EAE demonstrated superior modulation of inflammation-associated growth factors (IGFBP-5, HGF, Flt3L) and adipokines (leptin, resistin), indicating a broader therapeutic scope that includes metabolic dysfunctions. Collectively, our data reveal that EAE exerts a distinct immunoregulatory profile, modulating both innate and adaptive immune pathways while simultaneously addressing metabolic pathologies. These multifaceted actions underscore its promise as a phytotherapeutic candidate for the management of ulcerative colitis and other inflammatory conditions, with potential advantages over conventional steroid treatment. Full article

Background: Endometriosis, believed by many to be rooted in immunology, is a chronic disease. Upregulation of programmed cell death protein 1 (PD-1) in immune cells may compromise their defensive function, a mechanism demonstrated in the context of cancer spread. This study aims to explore the potential involvement of PD-1 in the pathophysiology and progression of endometriosis. A total of 62 patients who underwent laparoscopic surgery were analyzed, with 47 diagnosed with endometriosis and 15 serving as controls. We collected peritoneal fluid and peripheral blood samples during surgery and examined them using flow cytometry. Using a panel of monoclonal antibodies, the samples were stained and the expression of PD-1 in immune cells was evaluated. Results: We observed a statistically significant rise in the percentage of the CD56⁺ CD16⁺ NK cell subset expressing PD-1 within the peritoneal fluid of endometriosis patients compared to the control group (p = 0.021). Similarly, we found that PD-1 expression on immune cells significantly differed based on factors such as body mass index and smoking habits. Moreover, peritoneal subsets of PD-1⁺ T and NK cells showed an increase in patients presenting symptomatic endometriosis and those with more widespread disease. Conclusions: Our evaluation of the inhibitory PD-1 receptor has strengthened the potential connection between immune escape mechanisms often seen in cancer cells and those in endometriotic cells. This concept could pave the way for future research in the field of immunomodulation and endometriosis. Full article

Lung cancer is the most common cause of death due to cancer in the world, and non-small cell lung cancer (NSCLC) is the most common form of lung cancer, representing approximately 84% of all cases. Due to its frequency and mortality, the amount of research on this subject has been greatly increased and new techniques to improve health outcomes have been established. While surgery remains the gold standard of treatment, immunotherapy used alone or in conjunction with surgery shows promising results. This review aims to give an overview of current and new surgical and immunotherapy methods used for the treatment of NSCLC, as well as ways in which they can be combined and the clinical outcomes for patients with each treatment modality. Additionally, it will seek to highlight any gaps in current knowledge of treatment and propose further studies to improve the efficacy of NSCLC treatments. Full article

Neutrophils are an essential protective component of the innate immune system. However, in severe bacterial infections, neutrophils are known to mis-localise from the primary site of infection to other organs, where excessive release of cytokines, chemokines, and neutrophil extracellular traps (NETs) can induce organ damage and death. In this study, we use an animal model of bacterial infection originating in the peritoneum to show that hydrogen peroxide (H₂O₂, a potent neutrophil chemoattractant) is initially released in high concentrations both in the peritoneum and in multiple ‘off-target’ organs (lungs, liver and kidneys). The initial high H₂O₂ release inhibits neutrophil chemotaxis, but after 24 h concentrations of H₂O₂ reduce and can promote neutrophil migration to organs, where they release pro-inflammatory cytokines and chemokines along with NETs. The antimalarial compound artesunate potently inhibits neutrophil migration to off-target organs. It also abolishes cytokine, chemokine, and NET production, suggesting that artesunate may be a valuable novel therapy for preventing off-target organ inflammation associated with severe bacterial infections. Finally, the potency of H₂O₂ as a chemoattractant is shown by in vitro experiments in which, faced with competing gradients of H₂O₂ and other chemoattractants, neutrophils preferentially migrate towards H₂O₂. Full article

Immune cells like neutrophils, monocytes/macrophages, and lymphocytes play key roles in the development, progression, and resolution of deep vein thrombosis (DVT) by contributing to inflammation, coagulation, and fibrinolysis. IFN-γ, a cytokine mainly secreted by natural killer (NK) and T cells, is a critical factor in DVT pathogenesis. It links immune responses to coagulation activation by promoting endothelial activation, leukocyte recruitment, cytokine release, and coagulation imbalance. Its strong pro-inflammatory and prothrombotic effects make IFN-γ a promising target for DVT treatment beyond standard anticoagulants. Exploring ways to block IFN-γ signaling or its downstream effects could open doors to novel therapies for DVT, aiding in resolution and preventing post-thrombotic complications. This review delves into DVT pathophysiology, diagnostics, and management, emphasizing the importance of targeting immune cells and IFN-γ to advance treatment options. Full article

Cardiomyopathies affect over 3 million individuals globally, with conventional treatments exhibiting up to 60% resistance and 25% 30-day readmission rates. This review synthesizes the current evidence on the role of neuro-immune interactions in the pathogenesis of cardiomyopathy and evaluates emerging therapies targeting this axis. We systematically examined clinical trials and mechanistic and multi-omics data across cardiomyopathy phenotypes, focusing on autonomic-immune dysregulation. Sympathetic overactivation, present in approximately 85% of patients, correlates with elevated pro-inflammatory cytokines (TNF-α, IL-1β, and IL-6) and contributes significantly to therapeutic non-response. Concurrent parasympathetic withdrawal impairs cholinergic anti-inflammatory pathways, as reflected by reduced heart rate variability and baroreflex sensitivity. At the molecular level, shared mechanisms include inflammasome activation, neuroimmune synaptic signaling, and neurogenic inflammation. Emerging therapies targeting this axis are promising. Vagus nerve stimulation, as demonstrated in the INOVATE-HF trial, improves functional outcomes, whereas IL-1β antagonists reduce cardiovascular events by 15–20% in the context of inflammatory diseases. Bioelectronic interventions, such as transcutaneous vagal nerve stimulation and baroreflex activation therapy, offer noninvasive dual-modulatory strategies that address both neural and immune pathways, positioning the neuroimmune axis as a central driver of cardiomyopathy, regardless of etiology. The integration of genetic and metabolomic profiling may enable precision therapies targeting neuroimmune circuits, thereby overcoming the limitations of hemodynamic-focused care. This mechanistic framework shifts the therapeutic paradigm from symptomatic relief to targeted modulation of pathogenic pathways, with implications for millions of patients with cardiomyopathy and broader inflammatory cardiovascular disorders. Full article

Inducible forms of chronic urticaria are characterized by an early age of onset and a long duration of disease. In addition, cold and cholinergic urticaria have a risk of developing systemic, sometimes life-threatening, reactions. Determining the pathogenetic mechanisms and laboratory and clinical predictors of their development is an open question in the understanding of these diseases. This literature review demonstrates the current known facts that allow the identification of patients with cold and cholinergic urticaria in high-risk groups of anaphylaxis development and, therefore, the possibility to prevent emergency situations and to manage them in time. For cold and cholinergic urticaria, observations of Kounis syndrome–acute coronary syndrome (myocardial infarction or unstable angina) have been described. A series of trials, including the large international multicenter COLD-CE study of anaphylaxis in cold urticaria, have identified early age of urticaria onset, severe clinical symptoms, shortening of the critical temperature threshold, comorbid bronchial asthma, concomitant angioedema, and pruritus of the earlobes as warning signs. No such large-scale studies have been conducted for cholinergic urticaria. Among the few high-risk factors for systemic reactions in cholinergic urticaria described in the literature is the occurrence of angioedema. Thus, it is possible to identify some patients in the high-risk group already at the stage of initial anamnesis collection, and additional data can be collected during the examination. Laboratory biomarkers, clinical predictors, understanding the mechanisms of anaphylaxis by physical triggers or their consequences, and optimal options for pathogenetic therapy are still unresolved issues that require further research. The aim of this review is to provide a content analysis of current knowledge about chronic inducible urticarias in order to increase clinicians’ awareness and, consequently, reduce the risk of urgent conditions associated with them. Full article

Addressing the critical challenge in the differential diagnosis of severe inflammatory lung diseases, we propose a novel methodology for the analysis of macrophage surface receptors, CD68 and CD206, using specific non-antibody ligands. We developed a non-antibody alternative for the fluorometric detection of CD68+ cells, focusing on macrophages as key functional markers in inflammatory processes. Our marker based on dioleylphosphatidylserine (DOPS), a specific ligand to CD68, was incorporated into a liposomal delivery system. The specificity of this DOPS-based ligand can be precisely modulated by the liposome’s composition and the polyvalent presentation of the ligand. We synthesized a series of fluorescently-labeled DOPS-based ligands and developed a liposome-based sandwich fluorometric assay. This assay enables the isolation and quantification of CD68 receptor presence from bronchoalveolar lavage fluid (BALF). The results confirmed the specific binding of DOPS/lecithin liposomes to CD68+ cells compared to control lecithin systems. Furthermore, the incorporation of PEGylated ‘stealth’ liposomes significantly enhanced binding specificity and facilitated the generation of distinct binding profiles, which proved valuable in differentiating various inflammatory conditions. This approach yielded unique binding profiles of PS-based ligands to CD68+ cells, which varied significantly among a broad range of respiratory conditions, including primary ciliary dyskinesia, bronchial asthma, bronchitis, bacterial infection, pneumonia, and bronchiectasis. Confocal Laser Scanning Microscopy demonstrated selective binding and intracellular localization of the DOPS-based marker within CD68+ macrophages from BALF samples of patients with bronchitis or asthma. The binding parameters of this multivalent composite ligand with the CD68 receptor are comparable to those of antibodies. The inherent binding specificity of phosphatidylserine may offer a sufficient and viable alternative to conventional antibodies. Our results demonstrate the remarkable potential of this novel DOPS-based assay as a complementary tool for the developing non-antibody-based systems for the differential diagnosis of the respiratory diseases, warranting further investigation in larger clinical studies. Full article

Rheumatoid arthritis synovial fibroblasts (RASFs) play a pivotal role in joint destruction in RA. Myostatin (MSTN), a myokine, is highly expressed in the RA synovium; however, its role in the function of RASFs is unclear. We hypothesized that MSTN amplifies inflammatory cytokines/chemokines, promotes RASF invasion, and facilitates CD4⁺ Th cell transmigration. Immortalized MH7A cells (RASFs) and healthy synovial fibroblasts (HSFs) were treated with MSTN (0, 10, 20 ng/mL) for 0, 24, and 48 h. Cytokines (IL-8, IL-17, TNF-α, IL-6, IL-23, IFN-γ, IFN-β) and chemokines (CCL2, CCL20, CXCL13, CXCL1) were quantified by ELISA, RT-qPCR, and Western blotting. To evaluate MSTN regulation, cells were treated with pro-inflammatory mediators (TNF-α, IL-17, IFN-γ, IFN-β, CCL2, CXCL1). MSTN’s effects on Thy-1(CD90)⁺ RASF/HSF proliferation, RASF invasion, and CD4⁺ T-cell transmigration were assessed. Compared with HSFs, RASFs exhibited greater proliferative activity. MSTN significantly upregulated cytokines/chemokines, with CXCL1 showing the strongest induction in RASFs. IFN-γ and IL-17 robustly increased MSTN expression, indicating a feed-forward loop. MSTN did not alter Thy-1(CD90)⁺ fibroblast proliferation but significantly enhanced RASF invasion and CD4⁺ T-cell transmigration. Neutralizing CXCL1 or IL-17 reduced transmigration, with stronger inhibition via CXCL1. These findings offer new insights into the role of MSTN in RA pathogenesis and highlight its potential as a therapeutic target. Full article

Type 1 diabetes mellitus (T1DM) is an autoimmune disease characterized by immune-mediated β-cell destruction, where interleukin-6 (IL-6) signaling plays a complex and context-dependent role. Tocilizumab, an IL-6 receptor (IL-6R) inhibitor, is effective in several autoimmune conditions, but its influence on the onset and progression of T1DM remains uncertain. This scoping review aimed to map current clinical, genetic, and mechanistic evidence linking IL-6/IL-6R signaling to T1DM risk and to identify key research gaps. Following PRISMA-ScR guidelines, PubMed, Embase, and Web of Science were searched for studies from 2005 to 2025 reporting associations between tocilizumab or IL-6R modulation and T1DM onset. Six studies were included: one case report describing T1DM onset during tocilizumab therapy in a genetically predisposed patient, one randomized controlled trial showing no significant β-cell preservation with tocilizumab, three Mendelian randomization analyses with conflicting findings on IL-6R signaling, and one mechanistic study showing enhanced IL-6 responsiveness in early-stage T1DM. Collectively, evidence remains fragmented and inconclusive, highlighting research gaps in the differential roles of IL-6 classic versus trans-signaling and the impact of genetic predisposition. Future prospective studies should clarify whether selective IL-6 trans-signaling blockade may offer safer, targeted strategies for modulating autoimmune β-cell destruction. Full article

Intrahepatic cholangiocarcinoma (iCCA) is a highly aggressive and heterogeneous malignancy characterized by marked resistance to standard chemotherapy and poor prognosis. While the advent of immunotherapy has revolutionized the management of several solid tumors, including melanoma, breast cancer, and non-small cell lung cancer, its efficacy in iCCA remains limited. Recent clinical trials have demonstrated the efficacy of durvalumab in combination with chemotherapy for iCCA, leading to its approval as a first-line treatment. However, overall response rates remain low, largely due to its immunosuppressive tumor immune microenvironment (TIME). The immune-cold nature of iCCA is typified by a dominant presence of immunosuppressive cell populations, including M2-polarized tumor-associated macrophages, myeloid-derived suppressor cells, and T regulatory cells. In addition, traditional biomarkers such as PD-L1 expression, tumor mutational burden, and microsatellite instability have shown limited predictive value in iCCA, highlighting the need for novel biomarkers and immunotherapeutic strategies. Emerging approaches aimed at reprogramming the TIME, including combination therapies targeting suppressive cells, stromal remodeling, and novel immune effectors like CAR-T and cancer vaccines, hold significant promise for enhancing therapeutic efficacy. This review summarizes the distinct features of iCCA TIME, key mechanisms of immune evasion, current challenges, and future directions to overcome immune resistance, with the aim of developing personalized immunotherapies to improve patient outcomes. Full article

Background/Objectives: Obesity induces chronic low-grade inflammation marked by elevated pro-inflammatory cytokines, such as interferon-gamma (IFN-γ), and reduced anti-inflammatory cytokines like interleukin-10 (IL-10), contributing to immune dysregulation. Intermittent fasting (IF) may restore immune balance through metabolic and circadian mechanisms. This study compared the effects of time-restricted eating (TRE) and alternate-day modified fasting (ADMF) on IFN-γ and IL-10 levels in young women with obesity. Methods: A 20-day quasi-experimental study with a pretest–posttest control group design included 23 non-diabetic women with obesity (aged 18–25 years; BMI ≥ 25 kg/m² according to the Asia-Pacific classification), randomized into control (n = 8), TRE 18:6 (n = 8), and ADMF (n = 7) groups. IFN-γ and IL-10 serum levels were measured pre- and post-intervention using ELISA kits. Results: TRE significantly reduced IFN-γ levels (p = 0.025), while no significant change was observed in the ADMF or control groups. No significant changes were found in IL-10 levels. Conclusions: TRE effectively reduced pro-inflammatory IFN-γ levels without significantly altering anti-inflammatory IL-10 levels, suggesting an anti-inflammatory effect primarily mediated through suppression of IFN-γ rather than IL-10 upregulation. The absence of significant IL-10 changes may reflect complex immunoregulatory dynamics in obesity. ADMF showed no significant immunomodulatory impact. These findings support TRE as a promising non-pharmacologic strategy to attenuate inflammation and improve immune balance in young women with obesity. Full article

Viral infection is a significant cause of morbidity and mortality following allogeneic hematopoietic stem cell transplantation (Allo-HSCT), largely due to its impact on and interaction with immune reconstitution. Both innate and adaptive immunity are essential for effective viral control, yet their recovery post-transplant is often delayed or functionally impaired. Emerging evidence suggests genetic variation, particularly polymorphisms in the IL28B gene (encoding IFN-λ3), as a critical factor influencing the quality and timing of immune responses during the early post-transplant period. This review explores the role of IL28B polymorphisms in shaping antiviral immunity, in general, as well as after Allo-HSCT. IL28B variants have been implicated in modulating interferon-stimulated gene (ISG) expression, natural killer (NK) cell activity, and type I/III interferon signaling, all central components of innate immune defense against viral infections. Furthermore, IL28B polymorphisms, particularly rs12979860, have been shown in both general populations and limited HSCT cohorts to alter T cell response and interferon production, affecting reactivation and clearance of multiple viruses such as cytomegalovirus (CMV), hepatitis B virus (HBV), hepatitis C virus (HCV), Epstein–Barr virus (EBV), COVID-19, and BK polyomavirus (BKPyV) as well as Graft vs. Host disease, thereby affecting adaptive immune reconstitution and long-term viral control. Understanding how IL28B genotype alters immune dynamics in transplant recipients could enhance risk stratification for CMV and other diseases and inform personalized prophylactic or therapeutic strategies. Therefore, this review highlights IL28B as a promising biomarker and potential immunoregulatory target in the management of viral infection post-Allo-HSCT. Full article

Crohn’s disease is a chronic, idiopathic inflammatory bowel disease characterized by patchy, transmural inflammation that is influenced by genetic, environmental, and microbial factors. The NOD2 pathway mediates NFκB activation and pro-inflammatory cytokine production. In the SHIP–/– murine model of Crohn’s disease-like ileitis, macrophage-derived IL-1β production drives intestinal inflammation. SHIP reduces NOD2 signaling by preventing downstream interaction between RIPK2 and XIAP, leading us to hypothesize that blocking RIPK2 in SHIP–/– mice would ameliorate intestinal inflammation. We examined the effects of RIPK2 inhibition on pro-inflammatory cytokine production in SHIP+/+ and SHIP–/– macrophages and in mice, using the RIPK2 inhibitor, GSK2983559. We found that GSK2983559 blocked RIPK2 activation in SHIP+/+ and SHIP–/– bone marrow-derived macrophages (BMDMs), and reduced Il1b transcription and IL-1β production in (MDP+LPS)-stimulated SHIP–/– BMDMs. Despite the reduction of IL-1β production in BMDMs, in vivo treatment with GSK2983559 worsened intestinal inflammation and increased IL-1β concentrations in the ileal tissues of SHIP–/– mice. GSK2983559 only modestly reduced IL-1β in (MDP+LPS)-stimulated SHIP–/– peritoneal macrophages, and did not suppress pro-inflammatory cytokine production in response to TLR ligands in peritoneal macrophages from either SHIP+/+ or SHIP–/– mice. Taken together, our data suggest that although RIPK2 inhibition can block IL-1β production by (MDP+LPS)-stimulated macrophages in vitro, it is not an effective anti-inflammatory strategy in vivo, highlighting the limitations of targeting RIPK2 to treat intestinal inflammation in the context of SHIP deficiency. Full article

Olive oil, a cornerstone of the Mediterranean diet, is increasingly recognized not only for its cardiovascular benefits but also for its potential role in cancer prevention and therapy. Among its bioactive constituents, several phenolic compounds—tyrosol, hydroxytyrosol, oleuropein, oleacein, and oleocanthal—have demonstrated promising anticancer activities in various experimental models. These compounds act synergistically through diverse mechanisms, including antioxidant, anti-inflammatory, and immunomodulatory effects, as well as modulation of cell proliferation, apoptosis, angiogenesis, and metastasis. Notably, oleocanthal selectively induces cancer cell death via lysosomal membrane permeabilization, while hydroxytyrosol and oleuropein exhibit potent radical-scavenging and anti-proliferative properties. This review synthesizes findings from in vitro, in vivo, and clinical studies on the anticancer potential of these polyphenols, with emphasis on their mechanisms of action and possible applications in cancer prevention and adjunctive therapy. Given the established link between obesity and cancer development, clinical studies examining the metabolic, anti-inflammatory, and immunomodulatory effects of olive polyphenols in populations with obesity or prediabetes provide valuable insights into their potential to influence cancer-related pathways indirectly. However, direct clinical evidence in cancer patients remains limited and preliminary, underscoring the need for focused, well-controlled trials with cancer-specific endpoints. Furthermore, it critically evaluates the translational relevance of these findings, highlighting gaps in clinical research and future directions. Literature was retrieved from Google Scholar, PubMed, and ScienceDirect using keywords such as cancer, immunomodulatory, anti-inflammatory, olive, tyrosol, hydroxytyrosol, oleuropein, oleacein, and oleocanthal. Given the rising global cancer burden and the favorable safety profiles of these natural molecules, elucidating their molecular actions may support the development of novel integrative therapeutic strategies. Full article

The immune response to SARS-CoV-2 infection involves significant alterations in the phenotype and function of natural killer (NK) cells. This study aimed to investigate the dynamic changes in NK cell subsets during COVID-19 by analyzing their activation and inhibitory markers [CD3, CD14, CD16, CD19, CD25, CD45, CD56, CD57, CD69, CD159a (NKG2A), CD159c (NKG2C), CD314 (NKG2D), CD335 (NKp46)], cytotoxic potential (perforin, interferon-gamma, granzyme B), and direct cytotoxicity against a newly genetically modified K562 cell line. Peripheral blood samples were collected from COVID-19 patients on days 3–5 and day 30 post-symptom onset and were compared to healthy controls. 16-color flow cytometry analysis revealed distinct shifts in NK cell subpopulations, characterized by increased expression of the inhibitory receptor NKG2A and the activating receptors NKG2D and NKG2C, particularly in the CD56⁺CD16⁻ subset. Elevated IFN-γ production on day 30 suggested a recovery-phase immune response, while the persistent upregulation of NKG2A indicated an ongoing regulatory mechanism. The CD16⁺CD56⁻ subpopulation exhibited increased expression of the markers CD69 and CD25 over time; however, its cytotoxic potential, assessed through granzyme B levels and direct cytotoxicity assays, remained lower than that of healthy controls. Significant correlations were observed between CD57 and CD69 expression, as well as NKp46 and IFN-γ production, highlighting a coordinated balance between activation and regulatory mechanisms. These findings suggest that NK cells undergo functional adaptation during COVID-19, displaying signs of partial exhaustion while retaining antiviral potential. Understanding the interplay between NK cell activation and suppression may provide valuable insights into immune dysregulation in COVID-19 and inform potential therapeutic interventions. Full article

The human C-C chemokine receptor type 5 (CCR5) is a molecule primarily expressed on the surface of inflammatory cells, acting as the main HIV co-receptor. In order to penetrate host cells, HIV interacts with both CCR5 and the CD4 molecule during the infectious process. Emerging evidence suggests that pollution by metals, such as aluminum, lead, and manganese, triggers CCR5-mediated inflammation, which may have important implications for the risk of HIV infection. Specifically, we hypothesize that exposure to pollution by metals causes inflammation and elevated CCR5 expression on the surface of CD4+ cells, resulting in an increased risk of HIV infection. Our hypothesis is supported by toxicogenomic data, which shows that both air pollutants and some metals (e.g., arsenic, cadmium, nickel) induce CCR5 expression. Finally, approaches to evaluate the hypothesis are suggested. If confirmed, our hypothesis introduces environmental pollution to the set of biological factors influencing the risk of HIV infection. Full article

The prostate gland, a male accessory reproductive organ, is regulated by hormonal inputs and autonomic innervation from the major pelvic ganglion. This study examined the effects of major pelvic ganglion denervation on prostate histology, immune cell infiltration, and systemic levels of prolactin, testosterone, and cytokines in rats. Male Wistar rats (300–350 g) were divided into groups receiving bilateral axotomy of the hypogastric nerve, the pelvic nerve, or both, alongside with a sham-operated control. After 15 days, the animals were killed, and prostate tissue was dissociated in DMEM medium containing DNase I and collagenase. The dissociated cells were stained with fluorochrome-conjugated antibodies, and cell characterization was performed using a flow cytometer. Hematoxylin and eosin (H&E) staining was used to analyze histological characteristics, while testosterone, prolactin, and interleukin levels were measured via ELISA. Histological analysis revealed inflammatory atypical hypertrophy e hiperplasia. Immunological assessments demonstrated increased leukocytes, T lymphocytes (CD4⁺ and CD8⁺), B lymphocytes, and macrophages following double nerve axotomy. Serum analyses showed elevated pro-inflammatory cytokines IL-1β, IL-6, and IFN-γ, as well as anti-inflammatory IL-10, in denervated animals. Hormonal assessments revealed significant increases in serum prolactin and testosterone levels after double axotomy. Loss of neural control may promote pathological prostate changes via inflammation and hormonal dysregulation, offering insights into neuroimmune and neuroendocrine mechanisms underlying prostate pathologies. Full article

Immunotherapy has revolutionized cancer treatment. Despite its success across various malignancies, a significant proportion of patients either fail to respond (primary resistance) or relapse after an initial response (acquired resistance). This review explores the different mechanisms underlying resistance to immunotherapy, including tumor-intrinsic factors such as loss of antigen presentation, genetic, and epigenetic mutations. It also examines tumor-extrinsic contributors, such as immunosuppressive cells in the tumor microenvironment, checkpoint molecule upregulation, and microbiome influences. A comprehensive understanding of resistance mechanisms is essential for improving patient selection, developing combination therapies, and ultimately enhancing the efficacy and durability of immunotherapeutic interventions. Full article