Search Results (2,635)

Immunologically active peptides (IAP) are important bioactive peptides with potential antioxidant, anti-inflammatory, and immunomodulatory properties. However, their application in broiler production has not been systematically evaluated. This study investigated the effects of dietary IAP supplementation on growth performance, carcass traits, meat quality, selected serum biochemical indices, and ileum inflammatory cytokine expression in broilers. A total of 180 one-day-old Ross 308 male broilers were randomly assigned to 3 dietary treatments with 6 replicates per group for 42 d: a basal diet (CON), and the basal diet supplemented with 500 g/t or 1000 g/t IAP. Overall treatment tendencies were observed for final body weight (BW) and average daily gain (ADG) (p = 0.100; p = 0.096), with numerically higher values observed in broilers receiving 500 g/t IAP. Dietary supplementation with 500 g/t IAP significantly improved feed conversion ratio (p < 0.05). Across increasing dietary IAP levels, significant quadratic responses were observed for final BW, ADG, and FCR (p < 0.05), indicating nonlinear responses to increasing IAP supplementation levels. In addition, serum superoxide dismutase (SOD) activity was significantly increased in broilers receiving 500 g/t IAP compared with the control group (p < 0.05), and a significant quadratic response was observed across dietary IAP levels (p < 0.05). Furthermore, dietary IAP supplementation significantly reduced ileum interleukin-1β (IL-1β) mRNA expression in the 500 g/t group (p < 0.05), and IL-1β expression exhibited a significant quadratic response across IAP supplementation levels (p < 0.05). In conclusion, dietary supplementation with IAP, particularly at 500 g/t, improved feed efficiency, increased serum SOD activity, and reduced ileal IL-1β mRNA expression in broilers without compromising carcass characteristics or meat quality. These findings indicated that IAP has potential as a functional feed additive for further evaluation in broiler production. Full article

Per- and polyfluoroalkyl substances (PFAS) are widespread environmental contaminants associated with adverse health effects, yet dermal exposure remains poorly characterized. This study evaluated the influence of vehicle and chemical structure on dermal absorption and skin barrier integrity using a reconstructed human epidermis model (EpiDermFT). Two C6 PFAS, perfluorohexane sulfonate (PFHxS) and perfluorohexanoic acid (PFHxA), were applied in three vehicles (acetone, water, and diethylene glycol monobutyl ether [DEGME]) at concentrations of 0–0.015% for 4 or 24 h. PFAS concentrations were quantified in tissue and receptor media, and skin barrier integrity was assessed using histological and immunological endpoints. Increasing exposure resulted in higher concentrations of PFHxS and PFHxA in both tissue and media across all vehicles, indicating dermal penetration and absorption. PFHxS exhibited greater tissue retention but only a few small, isolated changes in cytokine and gene expression and no significant effect on barrier integrity. In contrast, PFHxA induced increased expression of inflammatory mediators and alterations in skin barrier function. These findings indicate a divergence between dermal retention and biological activity. Overall, while the vehicle influenced PFAS transport, biological responses were more strongly associated with functional group. These results suggest that functional group-dependent toxicity is an important determinant of dermal PFAS effects and should be considered when characterizing PFAS dermal hazard and grouping structurally related compounds for assessment. Full article

Background and Objectives: Hereditary angioedema due to C1 inhibitor deficiency (HAE-C1INH) is a rare autosomal dominant disorder caused by mutations in the SERPING1 gene and is characterized by considerable clinical variability among affected individuals. Although genotype–phenotype correlations have been reported, data from populations with high consanguinity rates remain limited. Therefore, this study aimed to construct pedigrees of HAE-C1INH families harboring SERPING1 mutations and to investigate whether mutation type is associated with phenotypic characteristics, particularly age at disease onset and C1 inhibitor functional activity. Materials and Methods: Eleven HAE-C1INH probands and their families were followed up at the Allergy and Immunology Department of Internal Medicine, Ege University Faculty of Medicine. Of the 295 family members identified through pedigree construction, 109 had symptoms compatible with HAE-C1INH, and 53 of these symptomatic individuals had both a confirmed SERPING1 genetic result and an available C1-INH functional measurement. Pedigrees were created using the Progeny Pedigree Drawing Software (Progeny Genetics LLC, Delray Beach, FL, USA). Demographic data, disease characteristics, C1-INH function levels, and SERPING1 mutation types were obtained from patient files. Results: A total of 295 individuals (151 males and 144 females) from 11 HAE-C1INH families were identified through pedigree construction. The analytical cohort comprised 53 symptomatic individuals, of whom 7 (13.2%) were homozygous for the variant. Among heterozygous patients (n = 46), 27 (58.7%) had missense mutations, 7 (15.2%) had nonsense mutations, 7 (15.2%) had large deletions, and 5 (10.9%) had frameshift deletion mutations. Patients carrying missense mutations had significantly higher median C1-INH functional activity (28.5%) than those with other mutation types (14.1%) (p = 0.026), and the median age of disease onset was significantly later in the missense group (20 years) than in the non-missense group (8 years) (p < 0.001). Annual HAE attack frequency was also lower in the missense group (median, 12 vs. 48 attacks per year; p = 0.009). Conclusions: Exploratory individual-level analyses showed higher residual C1-INH functional activity and later symptom onset among individuals carrying missense SERPING1 variants than among those carrying pooled non-missense loss-of-function variants. However, familial clustering and the small number of independent families limit the strength and generalizability of these findings. Full article

Porcine reproductive and respiratory syndrome virus (PRRSV) remains a major threat to the global swine industry, and the continuous emergence of genetically diverse strains poses challenges to vaccine development. In this study, a lipid nanoparticle-formulated mRNA vaccine encoding the PRRSV GP5 protein was constructed, and its preliminary immunogenicity was evaluated in BALB/c mice. The full-length ORF5 gene was amplified and cloned into the pIVT5 vector to generate the recombinant plasmid pIVT5-GP5. GP5-mRNA was synthesized via in vitro transcription and transfected into Marc-145 cells to verify antigen expression. Indirect immunofluorescence assay showed specific fluorescence signals in GP5-mRNA-transfected cells, and Western blotting further confirmed the expression of GP5 protein. The GP5-mRNA was subsequently encapsulated into lipid nanoparticles to prepare the GP5 mRNA-LNP vaccine formulation. BALB/c mice were immunized intramuscularly to evaluate humoral and cellular immune responses. The GP5 mRNA-LNP vaccine induced a GP5-specific IgG response, and sera collected on days 28, 35, and 42 after the initial immunization showed detectable neutralizing activity against PRRSV. Flow cytometric analysis showed an increased proportion of CD3⁺CD4⁺ and CD3⁺CD8⁺ T-cell subsets in the spleens of immunized mice. In addition, splenocytes from GP5 mRNA-LNP-immunized mice produced higher levels of IL-2, IFN-γ, and IL-4 after PRRSV antigen stimulation. Because mice are not the natural host of PRRSV, these results indicate that the GP5 mRNA-LNP vaccine candidate induced both humoral and cellular immune responses in BALB/c mice, providing a preliminary immunological basis for further optimization and evaluation in pigs. Full article

Background. Stool microscopy and anti-Ascaris IgG serology assess different, but related biological domains. Joint interpretation can identify immunological exposure and intestinal egg shedding without assuming one or both markers are a measure of current infection independently. Objective. To develop a four-pattern paired-marker framework for anti-A. lumbricoides IgG and copromicroscopy results from adults in Kazakhstan and to assess the qualitative analytical concordance of two IgG enzyme-linked immunosorbent assays (ELISAs). Methods. The cross-sectional field study involved 1000 adult volunteers from Almaty and the region providing matched serum and stool samples. Sera were tested by MVA Group indirect anti-Ascaris IgG ELISA, and stool samples were examined by the Kato–Katz and Fülleborn methods. The binary outcome was classified into four pair patterns. All sera were further tested with a commercial ELISA (DRG), and qualitative concordance was calculated. Results. Anti-Ascaris IgG was found in 331 of the 1000 subjects (33.1%; 95% CI, 30.3–36.1%), while A. lumbricoides eggs were detected in 240 subjects (24.0%; 95% CI, 21.5–26.7%). The paired patterns were IgG-positive/egg-positive in 185 participants (18.5%), IgG-positive/egg-negative in 146 (14.6%), IgG-negative/egg-positive in 55 (5.5%), and IgG-negative/egg-negative in 614 (61.4%). IgG positivity was detected in 77.1% of subjects with detected eggs and 19.2% of subjects without detected eggs (odds ratio, 14.15; 95% CI, 9.96–20.09; p < 0.001). The MVA Group and DRG ELISAs agreed for 990 of 1000 specimens (99.0%; 95% CI, 98.2–99.5%), with positive and negative agreements of 98.2% and 99.4%, respectively (κ = 0.98). Conclusions. Serology and copromicroscopy showed a high association, but they are not interchangeable. The paired-marker paradigm clarified concordant and discordant patterns while retaining IgG as a marker of past or ongoing immune exposure and stool eggs as markers of shedding at the time of sampling. High inter-assay agreement suggests analytical consistency within this serum panel, but does not imply diagnostic accuracy for active ascariasis. Full article

Objective: Self-assembling peptide nanomaterials are increasingly investigated as modular platforms for vaccine delivery and immune modulation. However, their structure-dependent interactions with immune cells remain insufficiently defined, limiting their early evaluation as peptide nanomaterial. This study evaluated the physicochemical properties and immunological effects of three Sup35 G7-derived self-assembling peptide nanomaterials, G7, G7d, and G7d(PEG)HER2, with particular attention to innate immune compatibility and macrophage responses. Methods: The morphology and surface charge of the peptides were characterized by transmission electron microscopy and zeta-potential analysis. Their cytocompatibility was assessed in THP-1 macrophages, Jurkat T cells, and IM-9 B cells. Transcriptomic and proteomic analyses were integrated to identify immune-cell-specific molecular responses. Cellular uptake, apoptosis, cytokine secretion, and intracellular reactive oxygen species production were further examined in macrophages. In vivo immunization in BALB/c mice was conducted to assess systemic immunoglobulin responses. Results: G7 and G7d assembled into large crystalline aggregates with limited dispersibility, whereas PEGylated G7d(PEG)HER2 formed more uniform nanofibers. All three materials showed positive zeta potentials and relatively low cytotoxicity across the tested immune cell models. Among these cells, macrophages displayed the strongest molecular responses. Integrated transcriptomic and proteomic analyses revealed coordinated alterations mainly involving metabolic remodeling, redox homeostasis, proteasome activity, and mitochondrial-associated pathways, rather than predominant activation of classical pro-inflammatory signaling. Ultrastructural analysis confirmed intracellular uptake of assembled peptides and mitochondrial morphological changes without detectable apoptosis. Cytokine profiling showed reduced secretion of multiple cytokines and chemokines, while G7 induced higher intracellular reactive oxygen species than G7d and G7d(PEG)HER2. In vivo, G7d administration was associated with increased serum IgG levels, whereas G7 showed a moderate effect and G7d(PEG)HER2 exhibited minimal changes; IgM levels remained unchanged. Conclusions: Sup35 G7 based self-assembling peptides exhibit low acute toxicity but induce structure-dependent modulation of macrophage function. Differences in assembly morphology and surface modification may influence systemic humoral responses. These findings support the importance of physicochemical design in evaluating immune compatibility of peptide nanomaterial scaffolds. Full article

To explore the emerging role of natural ligands, specifically coumarin and curcumin, and their coordination with the transition metals ruthenium (Ru) and iridium (Ir) as photosensitizers (PSs) in photodynamic therapy (PDT) for cancer. This highlights the integration of natural compounds and transition metals to overcome limitations in photophysical properties, hypoxia tolerance, and clinical translation. Regarding PDT oncology, this examines an immunological effect on Ru/Ir complexes and natural ligand–metal hybrids. They induce immunogenic cell death (ICD) through reactive oxygen species (ROS) generation, calreticulin exposure, extracellular ATP release, and HMGB1 secretion. These damage-associated molecular patterns act as “danger signals” to recruit dendritic cells, prime CD8⁺ cytotoxic T-cells, and establish systemic antitumor immunity. This study compares natural ligand–metal complexes with conventional Ru(II)/Ir(III) complexes and clinical PSs to assess their translational potential as immune-activating agents in PDT oncology, as well as focusing on the integration of nanotechnology with natural ligand–metal complexes to enhance delivery, biocompatibility, and clinical translation. A narrative review was conducted of the literature published between 2010 and 2025 across multiple electronic databases, including WanFang Data, PubMed, ScienceDirect, Scopus, Web of Science, Springer Link, SciFinder, and CNKI, without language restrictions. Studies focusing on coumarin, curcumin, Ru(II), Ir(III), and PDT were analyzed. Extracted data included chemical structures, absorption and emission spectra, singlet oxygen yields, biological activities, and therapeutic outcomes. Comparative evaluation was performed between free natural ligands, their Ru(II)/Ir(III) complexes, and nanodelivery systems to assess efficacy, biocompatibility, and translational potential. Coumarin and curcumin exhibited intrinsic antioxidant, anti-inflammatory, and anticancer properties but were limited by short absorption/emission ranges, poor photostability, and low singlet oxygen yields, restricting preclinical application. Coordination with Ru(II) and Ir(III) significantly enhanced intersystem crossing, extended absorption into the near-infrared region, and improved singlet oxygen quantum yields (Φ_Δ up to ~0.78). These complexes demonstrated potent photocytotoxicity under normoxia and hypoxia, achieving IC₅₀ values in the nanomolar range, which indicated organelle-specific targeting (mitochondria, lysosomes, ER), induced ICD, and synergized with checkpoint blockade. Nanocarrier encapsulation further improved solubility and tumor selectivity, and reduced systemic toxicity. Coumarin- and curcumin-based Ru/Ir complexes represent promising next-generation or immune-activating PDT agents by combining natural pharmacological activity with superior photophysical performance. The ability to generate reactive oxygen species under hypoxia and achieve multimodal therapeutic effects positions them as strong candidates for clinical translation. Clinical approval of natural ligand–Ru/Ir complexes depends on rigorous safety, pharmacokinetic, and nanodelivery validation, but these complexes clearly extend PDT beyond local cytotoxicity toward durable immune protection. Future research should prioritize ligand engineering, nanotechnology integration, and translational models to bridge preclinical promise with safe and effective clinical applications. Full article

The major histocompatibility complex (MHC) represents a critical genetic locus that orchestrates adaptive immune responses through antigen presentation and T cell activation, characterized by exceptional polymorphism and species-specific diversity. In herbivores, MHC polymorphisms constitute fundamental determinants of resistance to parasitic, viral, and bacterial infections while serving as crucial indicators of genetic diversity and breeding value in animal populations. Recent advances in high-throughput sequencing technologies, single-cell omics, and population genetics have substantially advanced understanding of MHC gene structure, allelic polymorphism, evolutionary patterns, and associations with disease susceptibility and vaccine responsiveness. This comprehensive review systematically examines the structural characteristics and regulatory mechanisms of MHC genes, their associations with infectious disease resistance, their role in vaccine responses, and their practical applications in molecular breeding programs, conservation genetics, and immunological research. We identify current technical limitations and outline future research directions to establish a robust theoretical foundation for disease resistance breeding and immune regulation strategies in herbivore populations. Full article

Background: The immune landscape in head and neck squamous cell carcinoma (HNSCC) has been widely investigated. However, the crucial role played by the lymph node microenvironment in metastatic and non-metastatic HNSCC remains unknown. This systematic review aims to discuss the immunological crosstalk between the tumor and the nodal microenvironment and to describe the distribution of immune cells in metastatic and non-metastatic lymph nodes. Methods: A systematic review was conducted according to the PRISMA guidelines. PubMed, Scopus, and the Cochrane Library were searched for studies published between 1990 and 2025, with the final search performed in December 2025. Prospective and retrospective studies evaluating immune cell infiltration in metastatic and non-metastatic cervical lymph nodes were included, whereas studies focusing exclusively on non-cellular biomarkers and non-English publications were excluded. The risk of bias was assessed using the Newcastle–Ottawa Scale. The results were synthesized narratively, and no meta-analysis was performed. Results: The screening process identified 608 articles, of which 27 met our predefined inclusion criteria. These studies focused on macrophages, dendritic cells, neutrophils, natural killer cells, T helper cells, cytotoxic T cells, regulatory T cells, B cells, total lymphocytes, and surface markers. This systematic review provides a well-structured analysis of current knowledge on the impact of the innate and adaptive immune systems on the response against cancer cells and the recruitment of immune cells in lymph nodes. The most significant findings highlight the crucial role of antigen presentation in the antitumor response, particularly through the recruitment and activation of dendritic cells and subcapsular sinus macrophages in tumor-draining lymph nodes. It also presents in a fairly comprehensible manner that the density of mature dendritic cells, cytotoxic T cells, and B cells is higher in non-metastatic lymph nodes. Discussion: The lymph node microenvironment is highly enriched with immune cell infiltration, and their distribution between metastatic and non-metastatic lymph nodes can contribute to a better understanding of the underlying pathological processes. Particular attention should be given to the innate immune system cells and their implication in antigen presentation. Our findings suggest that identifying immunological profiles of lymph nodes may provide a rationale for treatment de-escalation protocols and raise the question of lymph node preservation in antitumor immune responses. However, the heterogeneity and bias assessment of the included studies warrant a cautious interpretation of these findings. Another important limitation is the limited number of studies comparing the immune microenvironment of primary tumors and lymph nodes. Full article

Conventional needle-based vaccination may cause tissue injury and increase the risk of cross-contamination between animals. This study evaluated the immunological effects of delivering an inactivated porcine circovirus type 2 (PCV2) vaccine using a needle-free jet injection system compared with needle injection in pigs. Immune responses were assessed using enzyme-linked immunosorbent assay (ELISA) for PCV2-specific antibody levels on days 7, 14, and 28 post-vaccination. Cellular architecture at injection sites and differential gene expression were analyzed using immunohistochemistry and transcriptome sequencing. Results showed that pigs receiving needle-free vaccination at 0.50 mL and 0.75 mL injection volumes exhibited higher PCV2-specific antibody responses than pigs receiving 1.0 mL needle injection. Needle-free vaccination also preserved dermal collagen fiber architecture, altered antigen-presenting cell distribution, and was associated with distinct activation of immune-related pathways, particularly those involved in leukocyte migration and cytokine-cytokine receptor interactions. These findings indicate that needle-free vaccination was associated with distinct PCV2-specific antibody responses and local immune microenvironment changes, supporting its potential as an alternative vaccine delivery strategy for swine PCV2 vaccination. Full article

The tea tree (Melaleuca alternifolia) essential oil (TTEO) exhibited in vitro antioxidant activities with an inhibition concentration (IC50) of 29.02 ± 0.57 µg/mL. This is due to its content of bioactive compounds; practically α-pinene (1.52%), eucalyptol (9.05%), 2-bornanone (57.94%), 1-dotriacontanol (1.82%), 1-decanol, 2-hexyl- (1.99%), and 1-heptatriacotanol (4.90%). Therefore, this research aimed to determine changes in growth, antioxidant capacity, immune functions, and disease resistance in Nile tilapia (Oreochromis niloticus) when fed on a low-fishmeal (FM) diet enriched with TTEO. Nile tilapia juveniles (14.6–15.9 g) were fed on a low-FM diet containing 0.0 (the control), 0.1, 0.15, 0.2, and 0.25 g TTEO/kg feed up to apparent satiety three times a day for 70 days. Following the feeding trial, fish were intraperitoneally injected with Aeromonas hydrophila, and fish mortality was recorded for an additional 10 days. It is noted that feeding the fish on 0.2 g TTEO/kg feed increased the feed intake as well as the growth indices. Marked declines in FCR values were seen in fish fed on 0.15–0.25 g TTEO/kg feed. However, fish fed on a diet with 0.2 g TTEO/kg feed exhibited highest enhancements in intestinal villi width/length and absorption area compared with other TTEO levels. No statistical (p > 0.05) differences were observed in glucose and cortisol levels among TTEO-fed groups, indicating no stress effects on fish. Conversely, ALT and AST activities in Nile tilapia declined significantly (p < 0.05), especially at 0.20 and 0.25 g TTEO/kg feed, with no difference (p > 0.05) between the two treatments. It is noted that high TTEO levels (0.2–0.25 g/kg feed) increased hepatic superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) activities as well as the mRNA expression of hepatic SOD, CAT, and GPx genes. Compared with other TTEO groups, feeding the fish with 0.2 g TTEO/kg feed showed higher alkaline phosphatase, lysozyme, complement C3, and ACH50 levels, along with marked increases in IL-8 and IL-10 genes expression and declines in the expression TNF-α, IL-1ß, HSP70, Caspase-3, and Caspase-9 genes. After A. hydrophila infection, fish fed on the control diet exhibited the highest mortality (76.7%), whereas fish fed on 0.2 and 0.25 g TTEO/kg feed were more resistant to bacterial infection, with mortality rates of 23.3% and 26.7%, respectively, with no difference (p > 0.05) between them. The results confirmed that dietary TTEO enhanced growth, antioxidant capacity, immunological biomarkers, and disease resistance in Nile tilapia when added to low-FM diets, with an optimum dose of 0.2 g TTEO/kg feed. Full article

Immune checkpoint inhibitors (ICIs) targeting PD-1/PD-L1 have improved outcomes across squamous cell carcinomas (SCCs) of the head and neck, lung, esophagus, and skin, yet durable responses remain confined to a subset of patients in every subtype. Objective response rates vary substantially across SCCs despite overlapping genomic alterations, comparable tumor mutational burden, and high PD-L1 expression, indicating that tumor-intrinsic biomarkers alone do not explain this variability. Growing evidence points to the tumor immune microenvironment, and in particular the myeloid compartment, as a critical determinant of immunotherapy responsiveness. In this review, we synthesize current evidence on myeloid-mediated immune regulation across SCC subtypes, focusing on tumor-associated macrophages, myeloid-derived suppressor cells/tumor-associated neutrophils, and dendritic cells, and the mechanisms by which these populations impair antigen presentation, restrict T cell infiltration, and sustain immunologically “cold” tumor states. We further examine therapeutic strategies aimed at reprogramming rather than simply depleting suppressive myeloid populations, including radiation therapy, STING agonism, and myeloid-targeted agents (CSF1R, PI3Kγ, and CXCR2 inhibition), each of which has shown encouraging preclinical and early clinical activity in combination with ICI. Collectively, this evidence supports a model in which the myeloid compartment functions as an actionable, convergent determinant of ICI resistance across SCC subtypes, rather than merely a passive biomarker. We propose that through the integration of spatial and single-cell profiling of myeloid states with clinical history it will be possible to predict response to immune checkpoint therapy and personalize myeloid-directed combination strategies, though the specific biomarkers needed to match individual patients to a given myeloid-targeted approach remain to be defined. We further discuss the toxicity considerations associated with both immune checkpoint blockade and radiation-based combination approaches, the early-phase status of most myeloid-targeted agents currently in clinical development, and the extent to which mechanistic insight, derived predominantly from HNSCC, generalizes to squamous cell carcinomas arising at other anatomic sites. Full article

Human metapneumovirus (hMPV) is an important respiratory pathogen and a major cause of respiratory tract infections, particularly among vulnerable populations. Although hMPV was identified in 2001, it remains less extensively studied than other major respiratory viruses, such as influenza virus and respiratory syncytial virus (RSV), hindering the development of effective preventive and therapeutic strategies. This review examines the primary mechanisms by which hMPV evades host immune responses. The virus disrupts early innate immune signaling pathways, particularly those involved in the induction and signaling of antiviral interferons (IFNs) and modulates inflammatory responses. At the level of adaptive immunity, hMPV impairs T-cell activation and the development of long-lasting immunological memory, which may contribute to susceptibility to reinfection. The virus also alters the functions of several immune and structural cell types, including macrophages, dendritic cells, and respiratory epithelial cells. In addition, hMPV may modulate host microRNA expression to promote immune evasion and prolong infection. The recurrent nature of hMPV infections highlights the need to further investigate the immune-evasion mechanisms. Such research is essential for developing safer and more effective vaccines, antiviral agents, and immunomodulatory therapies. Full article

Dysregulation of the kynurenine pathway (KYNP) is increasingly recognized as a hallmark of cancer-associated metabolic reprogramming, contributing to immune evasion, oxidative stress, and tumor progression through the activity of enzymes such as indoleamine 2,3-dioxygenase 1 (IDO1), indoleamine 2,3-dioxygenase 2 (IDO2), and tryptophan 2,3-dioxygenase (TDO2). This systematic review aimed to evaluate the current evidence on the ability of phytochemicals to modulate the KYNP and their potential implications for cancer prevention and therapy. The review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and included English-language articles and book chapters published between 2016 and 2026 that were retrieved from the Scopus and PubMed databases. A keyword co-occurrence network was generated using VOSviewer (v1.6.20) based on the complete Scopus and PubMed exports of the included studies to identify major research themes. The available evidence indicates that phytochemicals restore anticancer immunity by targeting multiple components of the KYNP, including inhibition of IDO1-mediated kynurenine production and suppression of downstream aryl hydrocarbon receptor signalling, thereby enhancing cytotoxic T-cell responses, reducing immunosuppressive cell populations, and improving antitumor immune activity. Collectively, these findings support the KYNP as a promising immunometabolic target and highlight phytochemicals as potential complementary agents for cancer immunotherapy while emphasizing the need for further investigation of the biological and immunological roles of IDO2. Full article

Philadelphia-negative (Ph-negative) myeloproliferative neoplasms (MPNs) include polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF), which are clonal hematopoietic disorders caused by somatic gene mutations in the JAK2, CALR, or MPL genes. Mutations activate the JAK–STAT pathway and disrupt NF-κB signaling, leading to a chronic inflammatory state caused by pro-inflammatory cytokines and reactive oxygen species (ROS). This altered microenvironment causes serious clinical features of the disease, such as bone marrow fibrosis, splenomegaly, vascular niche remodeling, and a greater probability of thrombosis or secondary leukemic transformation. Concurrently, MPNs cause both severe immune dysregulation and tumor evasion, as evidenced by progressive lymphopenia, T and B cell exhaustion, Natural Killer cell maturation arrest, and the accumulation of myeloid-derived suppressor cells. Although FDA-approved JAK1/JAK2 inhibitors ruxolitinib, fedratinib pacritinib and momelotinib effectively reduce splenomegaly and symptom burden and have demonstrated survival benefits in clinical trials, their ability to eliminate malignant clones or induce durable disease modification remains limited, and disease progression continues to occur in most patients. Finally, this review assesses the complex immunological dysfunction and chronic inflammatory dysregulation that characterize Ph-negative MPNs, as well as emerging therapeutic strategies, emphasizing the importance of fully understanding these intricate microenvironmental mechanisms for the identification and development of novel precision treatment targets. Full article