Search Results (2,826)

Feline bocavirus (FBoV) is an emerging enteric virus associated with gastrointestinal diseases in cats and has attracted increasing attention in feline health. However, no commercial vaccine is currently available for the prevention and control of FBoV infection. VP2 is the major capsid protein of FBoV and represents a promising target for vaccine development. In this study, the FBoV VP2 protein was expressed using the insect baculovirus expression system. The purified VP2 protein self-assembled into virus-like particles (VLPs), which were formulated with Alum, ISA 206, or GEL 02 adjuvants to prepare VP2 VLP vaccines. The immunogenicity, cellular immune responses, antigen uptake, biodistribution, germinal center responses, and safety of the vaccines were evaluated in BALB/c mice. The results showed that all VP2 VLP vaccine formulations induced VP2-specific IgG antibodies and neutralizing antibodies, promoted B- and T-lymphocyte activation, enhanced dendritic cell maturation, and stimulated germinal center-related immune responses. Among the tested formulations, VP2+GEL 02 induced the strongest immune responses and showed favorable safety in mice. These findings demonstrate that FBoV VP2 exhibits favorable immunogenicity and represents a promising vaccine antigen for further development against feline bocavirus. Full article

Background/Objectives: Epstein–Barr virus (EBV) is a ubiquitous pathogen responsible for significant malignancies and autoimmune diseases, yet no prophylactic vaccine is available. The viral entry glycoproteins gL/gH and gB are essential for infection, but soluble forms are poorly immunogenic and fail to elicit durable neutralizing antibodies. Moreover, EBV infects both B cells and epithelial cells, demanding broad neutralization. This study aimed to develop a virus-like particle (VLP) platform that displays gL/gH and gB in a dense, repetitive array to overcome these barriers. Methods: We conjugated recombinant gL/gH and gB to Acinetobacter phage AP205 VLPs using SpyTag/SpyCatcher covalent linkage, generating monovalent and bivalent chimeric nanoparticles (co-displaying both antigens on the same particle). Mice were immunized with these VLP constructs or alum-adjuvanted soluble proteins, and antibody responses, neutralization titres against B-cell and epithelial-cell infection, as well as germinal centre responses and durability, were assessed over a four-month period. Results: AP205-conjugated nanoparticles elicited significantly higher antigen-specific IgG titres than soluble proteins. The chimeric VLP, co-displaying gL/gH and gB, induced the stronger neutralising antibodies, effectively blocking EBV entry into both B cells and epithelial cells. Mechanistically, VLP immunization drove robust and sustained germinal centre reactions, resulting in increased plasma and memory B cells, and maintained neutralising activity for at least four months. Conclusions: Precision nanoscale assembly of EBV entry glycoproteins on a synthetic VLP programs high-magnitude, broad-spectrum, and durable humoral immunity. The AP205-SpyTag platform offers a versatile and promising strategy for developing an effective prophylactic EBV vaccine. Full article

Chronic hepatitis C virus (HCV) infection is an established risk factor for B-cell lymphoproliferative disorders and represents a paradigmatic model of infection-driven lymphomagenesis. Although direct-acting antivirals have markedly reduced the burden of HCV-related disease, HCV-associated lymphomas continue to occur. Moreover, HCV screening remains incomplete in some geographical areas and healthcare settings, leaving a substantial proportion of infected individuals unaware of their status. This narrative review integrates current evidence on the mechanisms linking chronic HCV infection to mixed cryoglobulinemia and overt B-cell non-Hodgkin lymphoma. HCV lymphotropism and persistent antigenic stimulation could initially promote the selection and expansion of autoreactive B-cell clones, while mixed cryoglobulinemia represents the most informative pre-lymphomatous risk condition. Cytokine-mediated survival signals, particularly those involving B-cell activating factor, reinforce clonal persistence and cooperate with host genetic susceptibility, impaired apoptotic control, and activation-induced cytidine deaminase-mediated genomic instability. The progressive acquisition of somatic driver mutations, copy-number alterations, and epigenetic and transcriptomic changes may enable selected clones to escape functional anergy and become increasingly independent of the original viral stimulus that, in turn, represents an initial trigger of the lymphoproliferative process. Recurrent abnormalities converge on NF-κB, NOTCH, chromatin-regulatory, apoptotic, and cell-cycle pathways, although HCV-associated lymphomas remain molecularly heterogeneous. Emerging microRNA profiles further contribute to the molecular characterization of the transition from chronic infection and cryoglobulinemia to lymphoma. Despite the availability of highly effective antiviral therapies, HCV-associated lymphomagenesis remains clinically relevant and continues to provide an especially informative model for understanding how chronic viral infection can drive human cancer development. Full article

Background/Objectives: Infection with Bordetella pertussis causes whooping cough. CD4⁺ T cell responses depend on bacterial peptides displayed by HLA class II, yet allele- and strain-resolved maps of naturally processed B. pertussis HLA-DR ligands remain limited. We sought to define which antigens yield HLA-DR ligands in a human macrophage model and whether presentation is skewed by HLA-DR molecule and bacterial strain. Methods: THP-1–derived macrophages were pulsed with whole-cell lysates of B. pertussis vaccine/reference strain Tohama I or clinical isolate D420. HLA-DR was immunoaffinity purified; eluted peptides were identified by LC-MS/MS and assigned to HLA-DR molecules encoded by HLA-DRB1*01:01, HLA-DRB1*15:01, and HLA-DRB5*01:01. Results: We identified 63 B. pertussis peptide ligands from 29 source proteins. Presentation was skewed by HLA-DR molecule: DRB1*01:01 accounted for 37 ligands from 21 antigens, DRB1*15:01 for 22 from 7, and DRB5*01:01 for 4 from 4. Most source proteins contributed ligands primarily to one HLA-DR molecule, so an antigen that supplies peptides to one DR product need not supply peptides to another. Strain further partitioned the ligandome: 32 ligands unique to Tohama I, 12 to D420, and only 19 from 8 proteins with both lysates. Only three antigens contributed ligands to both DRB1*01:01 and DRB1*15:01; two of these, pertactin and filamentous hemagglutinin, are components of current acellular pertussis vaccines. Conclusions: B. pertussis HLA-DR ligandomes are jointly shaped by bacterial strain and HLA-DR molecule. Antigens can interact selectively with individual HLA-DR products, and peptides from a given antigen may be recovered after pulse with one strain but not another. These findings support HLA-DR and strain-aware interpretation of class II presentation and nominate BrkA autotransporter (Bordetella resistance to killing A), outer membrane protein A (OmpA), tracheal colonization factor (TcfA), and a divalent metal transporter (DMT) family transporter for follow-up. Full article

Background/Objectives: Antimicrobial peptides (AMPs) are considered alternatives to classical antibiotics due to limited resistance development in bacteria. However, bacteria can develop resistance to AMPs through evolutionary adaptation, including oligosaccharide modifications and multidrug efflux pumps. Further research is needed to elucidate the defense mechanisms employed against AMPs to address the emerging resistance problem. Pexiganan is a cationic peptide with effective broad-spectrum antimicrobial activity. The aim of this study is to elucidate the genomic and transcriptomic basis of E. coli’s evolutionary adaptation to pexiganan. Methods: The E. coli ATCC BAA-2523 strain became resistant to pexiganan via evolutionary adaptation methodologies. Whole-genome and transcriptome analyses of resistant and susceptible populations were conducted using Nanopore sequencing and Illumina RNA sequencing, respectively. Results: Resistance development became particularly evident after 15 µg/mL, and the bacteria demonstrated the ability to grow even at high doses (up to 1000 µg/mL). Increases in expression levels of classical ARGs such as emrB, acrF, OXA, sul2, and dfrA14 in the pexiganan-resistant strain indicate that bacteria have the potential for broad-spectrum resistance to other antibiotics alongside pexiganan. Missense mutations have been identified in the phosphatidylserine synthase and cardiolipin synthase genes, which are involved in membrane biosynthesis. Increased expression was observed in the membrane-bound lytic murein transglucosylase (mltF), the murein hydrolase activator (EnvC), and the Antigen 43 (Ag43) gene. Conclusions: Pexiganan may not only target the cell membrane but also trigger the bacterium’s overall transcriptional response and cross-resistance and MDR systems. Upregulation of multidrug efflux pumps, lytic murein transglucosylase, the murein hydrolase activator and the Antigen 43 gene might be associated with resistance. In addition, the missense mutation was detected in the membrane biosynthesis genes pssA and clsB. In vivo infection models, targeted functional genomics, and comprehensive phenotypic cross-resistance testing will be required to validate our results. 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

Ankylosing spondylitis (AS) is a chronic inflammatory disease strongly associated with human leukocyte antigen B27 (HLA-B27). However, the incomplete penetrance of HLA-B27 suggests that additional molecular mechanisms contribute to AS pathogenesis. Circular RNAs (circRNAs) have emerged as important regulators of immune responses, but their roles in AS pathogenesis remain incompletely understood. In this study, circRNA expression profiles were examined by high-throughput RNA sequencing and selected circRNAs were validated by quantitative RT-PCR in T cells from AS patients and healthy controls. Among the validated circRNAs, circRNPS1 was significantly up-regulated in T cells from AS patients. Overexpression of circRNPS1 in activated Jurkat cells increased IL-2, IL-17A, and interferon-γ expression and enhanced JAK2/STAT1 and MEK1/2-ERK signaling. RNA pull-down followed by proteomic analysis identified heterogeneous nuclear ribonucleoprotein K (hnRNPK) that binds to the back-splicing junction region of circRNPS1. CircRNPS1 increased the stability of hnRNPK and VAV1, whereas hnRNPK knockdown attenuated circRNPS1-mediated MEK1/2-ERK activation and inflammatory cytokine expression. Furthermore, an antisense RNA fragment targeting the back-splicing junction region of circRNPS1 suppressed IL-2, IL-17A, and interferon-γ expression in activated circRNPS1-overexpressing Jurkat cells and T cells from AS patients. Disrupting the interaction between circRNPS1 and hnRNPK therefore warrants further investigation as a potential therapeutic strategy for AS. Full article

Background: Mammalian arachidonic acid lipoxygenases (ALOXs) are non-heme iron-containing enzymes that oxygenate polyunsaturated fatty acids (PUFAs) with at least two isolated double bonds to hydroperoxy derivatives. The patho-physiological roles of these enzymes in inflammatory, hyperproliferative, and neurological diseases have made them promising targets for pharmacological interventions. Unfortunately, the expression levels of ALOX isoforms in mammalian cells are very low, which makes functional characterization of native enzymes and the development of isoform-specific inhibitors challenging. Methods: Here, we developed a unifying experimental protocol for fed-batch fermentation of mammalian ALOX isoforms in a bioreactor, followed by purification of the recombinant proteins and their functional characterization. Results: Our methodological protocol allowed the preparation of mg amounts of catalytically active human ALOX15, mouse Alox15 and human ALOX15B. The purified proteins are suitable for high-throughput inhibitor screening assays but can also be used as antigens for the preparation of isoform-specific antibodies and for direct structural analyses. Antibodies cross-reacting with human ALOX15 and ALOX15B have been detected in the blood of patients suffering from colorectal cancer. Conclusions: Our functional ALOX data stresses the catalytic differences between mouse and human ALOX15 orthologs, and these catalytic peculiarities need to be considered when the results of mechanistic studies obtained in mouse models of human diseases are transferred to the human situation. Full article

Triple-negative breast cancer (TNBC) is characterized by marked immune microenvironment heterogeneity and variable chemotherapy response, yet the epithelial transcriptional programs governing cytotoxic immune activation remain poorly understood. We performed an exploratory, integrative analysis using single-cell RNA sequencing of 31,962 cells from eight TNBC patients operationally stratified into Good and Bad Prognosis groups based on pathological lymphoid infiltration, a discovery grouping subsequently validated against pathological complete response (pCR) in three independent bulk RNA-seq cohorts. This analysis identified four epithelial transcriptional states. The G5 DNA damage subpopulation—predominantly restricted to Good Prognosis tumors (29.2% vs. 0%)—and the G4 Metabolism subpopulation—2.4-fold enriched in Bad Prognosis—were the primary prognostic signatures. Machine learning validation using nested leave-one-cohort-out (LOCO) cross-validation across 614 samples demonstrated that G4 + G5 raw genes with random forest yielded the largest observed mean AUC of 0.653, though these results are exploratory and do not establish a validated clinical classifier. CellChat ligand–receptor interaction analysis revealed that G5 DNA-damage epithelial cells are the dominant immune activators in Good Prognosis TNBC, predominantly engaging CD8 cytotoxic T cells through MHC-I antigen presentation via HLA-A/B/C/E/F → CD8A/CD8B interactions, the highest-probability signaling pathway identified. Spatial transcriptomics independently validated significantly higher DNA damage and CD8 T-cell scores in Good Prognosis tissue. Together, these exploratory findings suggest a framework in which tumor-intrinsic DNA damage signaling is associated with MHC-I antigen presentation upregulation and CD8 cytotoxic T-cell engagement, supporting further investigation of this axis and its potential implications for combining DNA-damaging chemotherapy with immune checkpoint blockade in TNBC. Full article

Bovine coronavirus (BCoV) is a major cause of respiratory and enteric diseases in cattle, resulting in substantial economic losses to the global cattle industry. Next-generation epitope-focused vaccines require conserved neutralizing determinants to achieve broad protective efficacy across circulating variants. Here, we applied a reverse-vaccinology and immunoinformatics-guided strategy to identify conserved linear B-cell epitope candidates on the BCoV spike protein. Using ABCPred (16 aa; threshold score 0.51), 139 putative linear B-cell epitopes were predicted, and 10 candidates (B1–B10) were selected based on antigenicity, allergenicity/toxicity filters, and Shannon-entropy-based conservation (≥95%). Each candidate was displayed on Helicobacter pylori ferritin and TEM confirmed the formation of self-assembled nanocages. BALB/c mice (n = 6 per group) were subcutaneously immunized with 50 μg of each epitope–ferritin fusion protein emulsified 1:1 with Montanide ISA 201 in a prime–boost regimen (at a 14-day interval), and sera were collected 14 days after the booster immunization. All 10 constructs induced BCoV-specific binding IgG (endpoint titers ranging from 1:2667 to 1:11,733), but only B1, B2, B4, B6, B7, and B8 elicited detectable in vitro neutralizing activity against both representative strains, whereas B3, B5, B9, and B10 remained below the detection limit (<1:8). Neutralizing titers were 1:24–1:99 for the enteric strain XHD4 and 1:27–1:88 for the respiratory strain HXD1, with no significant difference observed between the two strains (p > 0.05). Overall, these findings identify six conserved B-cell epitope candidates capable of eliciting neutralizing antibody responses against both representative enteric and respiratory field strains, providing experimental evidence to support epitope-focused BCoV vaccine design. Full article

(1) Background: Bovine viral diarrhea virus (BVDV) is an economically important pathogen affecting cattle worldwide. The genetic diversity of BVDV-2 in buffalo remains poorly understood. This study aimed to elucidate the genomic and antigenic features of GX24, the first BVDV-2b isolate identified from dairy buffalo in China. (2) Methods: The virus was isolated from a rectal swab through three blind passages in MDBK cells and identified through immunofluorescence and RT-PCR. The near-complete genome was sequenced using the Illumina platform and subjected to phylogenetic and recombination analysis. B-cell epitopes and glycosylation sites were predicted using BepiPred-3.0, Epitope1D, DiscoTope-3.0, NetNGlyc-1.0, and NetO-Glyc-4.0. (3) Results: The 12,267-nt GX24 genome (GenBank: PX682047) was classified as BVDV-2b. Recombination analysis detected a putative recombination signal within the NS5A gene involving Chinese BVDV-2b and Italian BVDV-2a strains. Integrative analyses predicted conserved linear and conformational epitope clusters in the N- and C-terminal regions of the E2 protein. Spatial analysis indicated that several epitope residues may be masked by glycan shielding. (4) Conclusions: This study provides the first genomic evidence of a BVDV-2b isolate from dairy buffalo in China, suggesting that BVDV-2b may be present in this population. The putative recombination signal and antigenic characteristics offer valuable insights for the development of diagnostics and vaccine design in the future. Full article

B cell aplasia (BCA), the sustained depletion of circulating CD19-positive B cells, is the defining on-target, off-tumor consequence of anti-CD19 chimeric antigen receptor (CAR) T cell therapy. Despite its occurrence across all approved CAR T cell products and all responding patients, BCA has not been systematically reviewed as a standalone clinical and biological phenomenon. This review synthesizes data from landmark trials and real-world cohorts across B cell-acute lymphoblastic leukemia (B-ALL), large B cell lymphoma, follicular lymphoma, mantle cell lymphoma, and chronic lymphocytic leukemia to characterize BCA incidence, recovery kinetics, prognostic significance, and management implications. Anti-BCMA products, which mechanism of action differs fundamentally, depleting plasma cells rather than B cell precursors, are intentionally excluded from this review. BCA is observed in all responders and is consistently absent in non-responders across reported cohorts , making it a reliable pharmacodynamic marker of CAR T cell activity. Its prognostic significance is disease-specific: in lymphoma, BCA recovery does not predict relapse and durable remission is achievable independent of sustained aplasia; in B-ALL, early BCA recovery within six months is a robust independent predictor of CD19-positive relapse, while persistent BCA correlates with sustained remission. CD19-negative antigen-escape relapse occurs preferentially in the presence of intact BCA and high pre-infusion tumor burden. Combining BCA kinetics with bone marrow next-generation sequencing minimal residual disease assessment at day 28 and month 3 constitutes the most powerful post-infusion risk-stratification framework currently available. BCA is mechanistically dissociated from hypogammaglobulinemia: IgM declines rapidly and profoundly, IgA more slowly, while IgG—maintained by CD19-negative long-lived plasma cells—is the most preserved isotype. No B cell count threshold below which hypogammaglobulinemia becomes clinically significant has been established. Evidence-informed IVIG replacement thresholds are proposed, though no randomized trial data exist to support them, representing a critical gap requiring prospective investigation. Full article

Background/Objectives: Batai orthobunyavirus (BATV) is an emerging mosquito-borne zoonotic pathogen for which no licensed vaccine is currently available. The viral envelope glycoprotein plays an important role in viral attachment and host immune recognition, making it a potential target for rational vaccine design. Methods: In this study, an immunoinformatics-based framework was used to design and evaluate a multi-epitope vaccine candidate targeting the BATV envelope glycoprotein. Selected B-cell, cytotoxic T-lymphocyte (CTL), and helper T-lymphocyte (HTL) epitopes were assembled using appropriate linkers and a human β-defensin adjuvant. Population coverage and in silico immune simulations were conducted to evaluate the potential breadth and magnitude of immune response. Results: The final vaccine construct demonstrated favorable physicochemical characteristics, high predicted antigenicity (0.7959), and non-allergenic properties while maintaining favorable predicted structural characteristics and broad predicted population coverage (99.92%). Structural docking revealed a stable interaction between the vaccine construct and human TLR4, with a weighted docking score of −1194.8, suggesting favorable molecular recognition and receptor engagement. Normal Mode Analysis further supported the structural stability and conformational integrity of the vaccine receptor complex. Immune simulation predicted robust primary and secondary immune responses characterized by elevated IgM and IgG antibody production, sustained memory cell formation, and strong IFN-γ and IL-2 responses, indicating the potential to elicit balanced humoral and cellular immunity. Conclusions: This study presents a structurally optimized and validated multiepitope vaccine candidate against the emerging Batai orthobunyavirus. These computational findings identified a promising vaccine candidate for further investigation; however, its immunogenicity, safety, and protective efficacy before further vaccine development can be considered. Full article

Systemic lupus erythematosus (SLE) is a complex autoimmune disease with a strong genetic component, and lupus nephritis (LN) represents one of its most common and severe organ-specific manifestations. This review synthesises current evidence on the genetic architecture of SLE and LN, with a particular focus on identifying shared and distinct genetic susceptibility loci and highlighting knowledge and data gaps in highly burdened African populations. Across studies, most risk loci, including HLA-DRB1, TNFSF4, IRF5, STAT4, TNFAIP3, BANK1, BLK, ITGAM, and FcγR2A/FcγR3A, converge on key immune pathways such as antigen presentation, type I IFN signalling, B-cell activation, and immune complex clearance. The findings support a substantial genomic overlap between SLE and LN, with most variants contributing to systemic immune dysregulation rather than kidney-specific susceptibility. A limited number of loci, including PDGFRA, HAS2, and SLC5A11, have been implicated in renal involvement, while APOL1 G1/G2 risk variants are associated with renal disease progression and adverse kidney outcomes among individuals of African ancestry. Despite these advances, relatively few loci have been definitively linked to LN independent of SLE, reflecting both biological overlap and limitations in study design. Moreover, the existing literature is heavily skewed toward European, Asian, and admixed populations, with minimal representation of continental African cohorts. Given the high genetic diversity and disproportionate disease burden in African populations, this represents a critical knowledge gap. Improved inclusion of diverse populations, coupled with high-resolution genomic and functional studies, will be essential to refine causal variant identification and enhance understanding of disease mechanisms. Ultimately, insights into population-specific genetic risk may enable earlier identification of high-risk individuals and support the development of precision medicine strategies for SLE, specifically LN. Full article

Background/Objectives: Glioblastoma (GBM) remains a lethal primary CNS malignancy with limited response to immunotherapy. Adoptive cellular therapy (ACT) improves survival in preclinical models, yet tumors ultimately recur. While T cell exhaustion is a common mechanism of resistance, the contribution of dendritic cell (DC) dysfunction remains unclear. We aimed to define mechanisms of immune escape following ACT, focusing on DC function and the role of hypoxia. Methods: Using a murine glioma model (KR158B-luc), mice were treated with ACT consisting of tumor RNA-pulsed DC vaccines and adoptively transferred T cells. Tumor-infiltrating immune populations were analyzed by flow cytometry. DC function was assessed using T cell activation assays. Bulk RNA sequencing and gene set enrichment analysis were performed on sorted DCs. Hypoxia was modeled in vitro, and HIF1α was perturbed using CRISPR-mediated knock-out. Results: ACT significantly increased survival but did not prevent tumor recurrence. Escaped tumors contained abundant cytotoxic, non-exhausted T cells, indicating that T cell dysfunction was not the primary driver of recurrence under ACT. Instead, tumor-associated DCs exhibited impaired T cell activation despite preserved antigen uptake. Transcriptomic analyses revealed reduced antigen presentation and co-stimulatory signaling, alongside increased expression of tolerogenic factors. ACT-treated tumors demonstrated heightened hypoxia pathway activation, with elevated HIF1α expression in DCs. Hypoxia induced DC tolerogenic programs and reduced their ability to activate T cells, an effect partially reversed by HIF1α disruption. Increased immune infiltration and inflammation following ACT further amplified hypoxia signaling and enhanced DC tolerance. Conclusions: DC dysfunction is one of the key mechanisms of immune escape following ACT in glioma. Hypoxia-driven tolerization of DCs impairs sustained anti-tumor immunity, highlighting the hypoxia–DC axis as a promising therapeutic target to enhance immunotherapy efficacy. Full article