Search Results (621)

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

Background: Bariatric surgery improves metabolic health, but long-term transcriptomic remodeling of white adipose tissue (WAT) after Roux-en-Y gastric bypass (RYGB) remains incompletely defined. This study aimed to characterize longitudinal WAT gene-expression patterns after RYGB and prioritize candidate signatures of post-surgical adaptation using a publicly available dataset. Methods: We analyzed subcutaneous WAT transcriptomic data from women with obesity who underwent RYGB, with samples collected before surgery and at 2 and 5 years after surgery. Differential expression analysis was integrated with pathway enrichment, supervised machine-learning-based feature prioritization and classification, and SHAP-based model interpretation. Results: Differential expression and machine-learning analyses showed clear separation between baseline and post-surgery transcriptomic states. Pathway-level findings indicated reduced inflammatory and immune-related signaling, particularly across pathways related to phagosome function, lysosomal activity, antigen presentation, and host-defense responses after surgery. Gene-level analyses additionally suggested extracellular-matrix and metabolic remodeling. Machine-learning models distinguished baseline from post-surgery samples, while SHAP analysis identified genes with the strongest contributions to model predictions. Importantly, several statistically prioritized genes also showed high SHAP attribution, demonstrating concordance between univariate statistical significance and multivariate predictive relevance. This convergence suggests that the models captured biologically meaningful surgery-associated signals rather than purely data-driven classification artifacts. Conclusions: This study advances the interpretation of longitudinal adipose-tissue transcriptomic remodeling after RYGB by combining differential expression, pathway enrichment, supervised machine learning, and explainable AI within a unified framework. The integrated workflow prioritized candidate long-term remodeling genes, particularly immune/inflammatory and extracellular-matrix-related transcriptomic signatures, that warrant validation in independent cohorts. Full article

Background/Objectives: Renal ischemia–reperfusion injury (IRI) and infection-associated renal damage are characterized by persistent inflammation, oxidative stress, microvascular dysfunction, and impaired tissue regeneration, creating a hostile microenvironment that limits effective repair. We developed an injectable, photocrosslinkable methacrylated chitosan (CSMA) hydrogel for the localized co-delivery of cerium oxide nanoparticles (CeO₂NPs) and vascular endothelial growth factor (VEGF), aiming to integrate redox modulation, antibacterial activity, and regenerative support. Methods: Gelation, microstructure, rheology, degradation, and CeO2NP/VEGF were characterized. Tubular epithelial and fibroblast migration and endothelial network formation, angiogenic gene expression, and antibacterial activity against Staphylococcus aureus and Escherichia coli were evaluated in vitro. Theraputic performance was assessed by renal surface application in a rat renal IRI model and catheter-mediated interavsical administration in an ascending urinary tract infection model. Systematic biocompatibility was evaluated separately in a 14-day subcutaneous implantation study. Renal response were further investigated using transcriptomic and targeted molecular analyses. Results: The CSMA/VEGF/CeO₂NPs hydrogel exhibited rapid in situ gelation, interconnected porous architecture, stable viscoelasticity, gradual degradation, and sustained release of both CeO₂NPs and VEGF. The formulation enhanced tubular epithelial and fibroblast migration, promoted endothelial network formation and angiogenic gene expression and effectively inhibited both S. aureus and E. coli. In a surgically controlled rat renal IRI model, direct renal-surface application of the hydrogel reduced tubular injury, inflammatory infiltration, and fibrotic remodeling. In a separate ascending urinary tract infection model, catheter-based intravesical administration reduced the ascending renal bacterial burden and infection-associated inflammatory injury. No detectable adverse systemic effects observed under the tested conditions over the 14-day observation period in the subcutaneous implantation. Transcriptomic analyses further revealed that CSMA/VEGF/CeO₂NPs treatment was associated with marked remodeling of the renal injury microenvironment, characterized by suppression of antigen presentation and immune activation pathways, alongside restoration of metabolic programs associated with amino acid, lipid, and purine metabolism. These molecular changes were accompanied by downregulation of CIITA/CD74/MHC-II signaling, recovery of metabolic regulators AGXT and ACOX1, modulation of Hippo/YAP- and ECM-associated pathways, and preservation of renal structural markers including nephrin and WT1. Conclusions: The localized CSMA-mediated co-delivery of CSMA/VEGF/CeO₂NPs hydrogel promotes renal repair through resolution of maladaptive immune activation, metabolic reprogramming, angiogenic enhancement, and preservation of renal structural integrity, providing a promising biomaterial strategy for the treatment of ischemic and infection-associated renal injuries. Full article

Background/Objectives: High linear energy transfer (LET) carbon ions achieved more effective and biologically robust tumor control than photons in preclinical prostate cancer models; however, the longitudinal development of histopathological parameters remains insufficiently characterized, limiting the selection of the optimal treatment modality in patients. This study analyzed the temporal histological patterns after isoeffective photon, proton, and carbon ion irradiations. Methods: Two Dunning R3327 prostate carcinoma sublines (H, HI) grown subcutaneously in male Copenhagen rats received single-fraction isoeffective curative photon or carbon ion doses. For HI-tumors, the effectiveness of isoeffective curative proton doses and isoeffective subcurative photon and carbon ion doses was additionally investigated. Tumors were collected prior and up to 3 weeks after irradiation and processed for quantitative histology of proliferation (BrdU), DNA damage (γH2AX), hypoxia (pimonidazole), vascular (CD31), and immune cell (CD3, CD68) markers. Results: All modalities induced an early peak in γH2AX⁺ tumor cells and a pronounced suppression of BrdU⁺ cells, with more sustained effects after isoeffective carbon ions doses, particularly in the HI-tumors. These findings, however, differed strongly between hypoxic and oxic micro-environments. Vascular parameters, diffusion distances, and global and compartment-specific hypoxic fractions showed distinct temporal dynamics between photons and carbon ions in HI-tumors, whereas H-tumors exhibited more moderate and reversible changes. At curative carbon ion doses, there was a late rebound of BrdU-positive tumor cells and increased CD68⁺ macrophage accumulation in chronically hypoxic regions. CD3⁺ T cells showed a biphasic decrease-recovery pattern in HI-tumors largely independent of radiation quality and oxygenation. Conclusions: Longitudinal histology revealed modality- and tumor-line-specific trajectories of tumor, vascular, hypoxic, and immune responses after isoeffective photon, proton, and carbon ion irradiations in prostate carcinoma. The more persistent tumor cell damage and distinct vascular response, together with late proliferative and macrophage rebounds under chronic hypoxia after carbon ions, provide mechanistic support for the increased biological effectiveness and highlight hypoxia-driven repopulation and inflammation as key processes. Full article

Chronic hepatitis B (CHB) infection is a major risk factor for progressive cirrhosis and hepatocellular carcinoma. Persistent virus-induced inflammation alters liver function, leading to accelerated disease and increased mortality. Although lifelong treatment with nucleos(t)ide analogs (NAs) is highly effective at suppressing viral replication, covalently closed circular DNA (cccDNA) persists in hepatocytes to sustain chronic infection, underscoring the need for better interventions and combination therapies. The durable suppression of viral replication and restoration of immune responses through long-acting (LA) therapies offer a promising strategy for sustained HBV control. We transformed tizoxanide (TIZ), a broad-spectrum anti-infective and immunomodulatory agent, into a LA lipophilic prodrug formulation (NM2TIZ) for intramuscular or subcutaneous administration. NM2TIZ exhibited long-term stability during storage and was evaluated in AAV-HBV mice using monotherapy and combination therapy approaches with an LA tenofovir prodrug formulation (NM5TFV). NM5TFV reduced the HBV DNA levels by >2 log₁₀ fold. Furthermore, coadministration of NM5TFV with M2TIZ reduced the expression of liver inflammasomes and profibrotic markers. The NM5TFV and NM2TIZ combination reduced HBV replication, inflammation, and fibrogenesis in AAV-HBV-transduced mice. Full article

Virus-like particles (VLPs) based on the capsid protein (CP) of the ssRNA bacteriophage Beihai32 represent a promising nanoscale platform for the presentation of heterologous peptides. Previous studies have shown that the C-terminus of the CP tolerates long insertions without compromising VLP assembly. Here, we demonstrate that the N-terminus is similarly permissive to extended insertions. Hybrid CPs with one to four copies of the influenza A virus M2e peptide fused to the N-terminus were expressed in Escherichia coli. Fusion proteins containing four copies of M2e self-assembled into spherical VLPs, displaying the inserted peptides on the surface. Subcutaneous immunization of mice with chimeric VLPs induced high titers of M2e-specific antibodies. Unlike C-terminal fusions, the N-terminal insertion prevented the induction of anti-carrier antibody response indicting masking of the carrier protein in the chimeric VLP. To evaluate the capacity of the N-terminus for larger inserts, green fluorescent protein (GFP, 238 a.a.) was attached to the N-terminus of CP. The hybrid protein was expressed in Escherichia coli and formed VLPs. GFP was displayed on the particle surface and retained fluorescent activity. Overall, the phage Beihai32 CP is a versatile platform for the presentation of peptide antigens, supporting its potential application in VLP-based vaccine design. Full article

Background/Objectives: Pancreatic ductal adenocarcinoma (PDAC) is a lethal malignancy with a desmoplastic, immunosuppressive tumor microenvironment enriched in extracellular adenosine. High adenosine levels disrupt anti-tumor immunity by engaging adenosine receptors on T cells, macrophages, and dendritic cells. In this context, strategies to reduce extracellular adenosine signaling within the TME are in focus. Among them, enzymatic degradation of extracellular adenosine levels has emerged as a promising approach to overcome immune suppression and restore anti-tumor immune responses. Methods: Here, we engineered an E. coli strain to express a surface-bound form of a bacterial ADA2 enzyme and used the outer membrane vesicles produced by this strain as nanoparticles carrying the functional enzyme. Our data indicate robust surface expression and enzymatic activity of ADA2 on OMV particles. Results: In a PDAC subcutaneous flank tumor model, intratumoral administration of OMV-ADA2 particles was associated with significantly increased infiltration of CD8⁺ T cells and Granzyme B expression and concomitant decreases in collagen deposition and α-smooth muscle actin (α-SMA) positive stromal cells, suggesting modulation of the desmoplastic stroma. Conclusions: These findings support further investigation of OMV–bADA2 as a potential platform to modulate tumor metabolism and stroma, activate anti-tumor immunity, and serve as a carrier for co-delivery of additional anticancer modalities in PDAC. Full article

Global elimination of hepatitis C virus (HCV) infection requires not only direct-acting antivirals (DAAs) but also the development of a highly effective prophylactic and/or therapeutic vaccine. Background/Objectives: Our aim was to optimize the composition of the candidate vaccine against HCV by combining recombinant non-structural proteins and a DNA construct with a complex adjuvant. Methods: C57BL/6 and DBA/2J mice were immunized three times at 2-week intervals using different schemes. The viral antigens consisted of a mixture of NS3, NS5A, and NS5B proteins and/or recombinant DNA expressing NS3-NS5B polyprotein. As adjuvants, a complex adjuvant, a mixture of Polymuramil^® and Pyrogenalum^® (NOD1/NOD2 and TLR-4 agonists), or a CpG ODN adjuvant (TLR-9 agonist) were used. Results: The most efficient regimen was three subcutaneous administrations of the combined DNA, recombinant protein components, and a new complex adjuvant. This scheme elicited a robust immune response, characterized by high antibody titers, enhanced antigen-specific lymphocyte proliferation, and significant interferon-gamma (IFN-γ) secretion in both mouse lines. Furthermore, the complex adjuvant outperformed CpG ODN in stimulating both humoral and cellular immunity against the HCV antigens. The vaccine composition stimulated the formation of CD4⁺ memory T cells and decreased the relative frequences of suppressive Treg and MDSCs. Conclusions: The presented candidate vaccine induces a strong immune response to HCV proteins. The next step would be to validate the protective effect in cell culture and animal models. This would one the path to preclinical studies of this vaccine composition. Full article

Background/Objectives: We describe the rationale, design and evaluation of a novel feline combination vaccine (Nobivac^® NXT HCPChFeLV) incorporating RNA particle technology against feline leukemia virus (FeLV) alongside live attenuated components for feline herpesvirus-1 (FHV), feline calicivirus (FCV), feline panleukopenia (FPL) and Chlamydia felis. Efficacy and safety outcomes from laboratory and field studies are presented. Methods: Nobivac NXT HCPChFeLV is a 0.5 mL, non-adjuvanted, lyophilized vaccine containing live attenuated FHV, FCV, FPL, and C. felis strains, and an alphavirus replicon-derived RNA particle expressing FeLV envelope glycoprotein (gp85). The primary vaccination schedule involved subcutaneous vaccination at 8–9 weeks of age with a booster 4 weeks later. Onset-of-immunity studies were performed 1 week post primary vaccination. Duration-of-immunity studies evaluated challenge both at 1 year and 3 years after primary vaccination with a booster at 1 year (FHV, FCV, FeLV); FPL duration was assessed at 3 years after primary vaccination; C. felis duration was assessed at 1 year. Clinical signs of disease, survival, leukopenia (FPL) and pathogen excretion were assessed. Safety was assessed in laboratory overdose/repeat-dose studies and in a field study comparing concurrent (non-mixed) use with rabies vaccination vs a positive control regimen. Results: Vaccination significantly reduced clinical disease following FHV, FCV and C. felis challenge and reduced FHV-associated mortality. Vaccinated cats were protected from FPL clinical disease, mortality, leukopenia, and FPL excretion. Persistent FeLV antigenemia was significantly prevented after primary vaccination and in 1-year-duration-of-immunity studies and was reduced 3 years after revaccination. The excretion of FHV, FCV and C. felis was significantly reduced in vaccinates vs controls. No serious adverse events were observed in laboratory studies; field vaccination was well tolerated with no injection-site reactions reported. Conclusions: Nobivac NXT HCPChFeLV provides robust, long-lasting protection against multiple feline pathogens, reduced pathogen shedding and demonstrated a favorable safety profile, supporting its use in feline preventive healthcare. Full article

Medical ozone has emerged as a potential redox-modulating intervention in inflammatory and degenerative conditions, particularly in dermatological contexts characterized by chronic oxidative imbalance and impaired tissue remodeling. Unlike conventional pharmacological agents, ozone exerts its biological activity through rapid chemical reactions generating transient reactive and electrophilic species that activate endogenous adaptive signaling pathways. Controlled oxidative perturbations activate antioxidant transcriptional programs, primarily mediated by the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway, while modulating inflammatory signaling networks, including nuclear factor kappa B (NF-κB) and the NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome. This dual behavior reflects hormetic responses in which low-dose exposure promotes adaptive cellular signaling, whereas excessive oxidative burden leads to structural and functional damage. This review summarizes current knowledge on the molecular mechanisms underlying ozone-induced redox modulation, with emphasis on chemical reactivity, spatiotemporal signaling dynamics, thiol-based sensing, and metabolic reinforcement of antioxidant defenses. Particular attention is given to skin and subcutaneous adipose tissue, where oxidative stress, immune activation, and extracellular matrix remodeling converge. Dose dependency, safety constraints, and methodological variability are critically discussed, highlighting the narrow threshold between adaptive signaling and oxidative injury and the need for rigorous mechanistic and clinical validation. Full article

Cutaneous leishmaniosis (CL) remains a major neglected tropical disease, with current therapies constrained by toxicity, high cost, and variable efficacy. Here, we evaluated an immunochemotherapy strategy combining topical amphotericin B (AmB) with the therapeutic DNA vaccine HisAK70 in a murine model of Leishmania major infection. BALB/c mice were subcutaneously infected and treated with topical AmB cream alone, AmB plus HisAK70, or paromomycin (PM) as a reference therapy. Therapeutic efficacy was assessed through lesion progression, parasite burden in draining lymph nodes and spleen, and immunological markers associated with parasite control. Both PM and the combined AmB + HisAK70 treatment significantly reduced lesion progression and markedly decreased parasite burden compared with infected controls, demonstrating effective control of local infection and systemic dissemination. Importantly, the combination therapy enhanced the efficacy of AmB alone, supporting the beneficial contribution of vaccine-driven immune modulation to therapeutic outcome. Therapeutic efficacy was associated with reduced arginase activity in infected tissues and an increased IFN-γ/IL-4 ratio, indicative of a protective Th1-oriented immune response. Together, these findings highlight immunochemotherapy as a promising strategy for CL treatment, integrating localized topical drug delivery with targeted immune activation to improve therapeutic efficacy while potentially reducing systemic toxicity. Full article

Exposure to high altitudes for hours or days is defined as acute hypobaric hypoxia (AHH) condition, which rapidly engages adjustments such as signaling pathways involving inflammation, immune modulation and oxidative stress, whose dysregulation has been described as contributing to the pathophysiology of high-altitude illnesses, due to insufficient acclimatization, such as developing acute mountain sickness (AMS). Given its traditional high-altitude use and bioactive properties, Senecio nutans (S. nutans) extract, or chachacoma (CH), has emerged as a potential therapeutic strategy to mitigate high-altitude related pathobiology. The aim of this study was to evaluate the effects of S. nutans on acclimatization, regarding the status of oxidative stress, inflammation, immune and symptoms associated with AMS in an animal model exposed to AHH. Twenty-eight female Wistar rats (≈3 months old) were randomly allocated into four experimental groups (n = 7 each): normobaric normoxia (NX), normobaric normoxia plus S. nutans administration (NX+CH), acute hypobaric hypoxia (AHH; 48 h exposure), and acute hypobaric hypoxia plus S. nutans administration (AHH+CH). S. nutans was administered subcutaneously at a dose of 80 mg/kg, one hour prior to hypoxic exposure. Outcomes included body weight, food intake, hematological parameters, lung histopathology, pulmonary mRNA expression of HIF-1α, NF-κB, TNF-α, IL-1β, IL-6, and VEGF, and lipid peroxidation in lung tissue assessed by malondialdehyde (MDA) levels. After 48 h of AHH, animals exhibited a decrease in body weight and food intake, increase in hematocrit level and total leukocytes, as well as lung injury characterized by thickening of alveolar walls and inflammatory infiltrates. In addition, AHH induced an increase in pulmonary IL-6 and IL-1β mRNA expression. In contrast, S. nutans administration partially attenuated hypoxia-induced body weight loss, mitigated the rise in hematocrit levels, and reduced lung damage, while returning total leukocyte counts to control levels. Notably, S. nutans also decreased the hypoxia-induced overexpression of IL-6 and IL-1β. Regarding lipid peroxidation, no significant differences were observed among groups. These findings suggest that S. nutans exerts a protective effect against acute hypobaric hypoxia by attenuating inflammatory responses and preserving pulmonary structure, thereby supporting its potential as a preventive strategy to mitigate early pathophysiological alterations associated with high-altitude exposure. Full article

Objectives: Obesity disrupts adipose and systemic immune–metabolic homeostasis, yet the molecular mechanisms through which exercise restores abnormal tissue function remain incompletely defined. This study aimed to screen cross-tissue candidate genes associated with exercise-mediated correction of obesity-related transcriptional disorders via multi-tissue transcriptome profiling and bioinformatic gene prioritization. Methods: Transcriptomic datasets of mouse visceral white adipose, subcutaneous white adipose and skeletal muscle were downloaded from the public GEO database, covering normal control, high-fat induced obese and post-exercise intervention groups. R programming was applied to complete differential analysis, GO/KEGG enrichment, PPI network, LASSO and GSEA; independent human adipose datasets from GEO validated candidate genes. Results: Exercise reversed obesity-triggered transcriptional changes in adipose tissues. Exercise-responsive genes concentrated on immune inflammation, lipid and energy metabolism. Key hub genes for tissue remodeling were screened, and depot-specific pathway regulation was verified by GSEA. CCL2 showed consistent expression trends across mouse and human adipose data. Conclusions: This study identifies distinct tissue-specific transcriptional responses to exercise: visceral adipose mainly achieves reversal of obesity-induced inflammatory dysregulation, subcutaneous adipose undergoes combined immune–inflammatory and metabolic reprogramming, while skeletal muscle presents only energy-metabolism adaptive remodeling without obvious reversal of obese gene disorders. Immune–metabolic pathways dominate exercise-induced restoration in adipose tissues. Integrated network screening and cross-species validation identified CCL2 as a conserved candidate associated with exercise-responsive immune–metabolic pathways, providing valuable molecular candidates for further anti-obesity research. Full article

Background: Non-small-cell lung cancer (NSCLC) is the leading cause of cancer-related mortality worldwide. Although immune checkpoint inhibitors (ICIs) have significantly improved clinical outcomes, most patients do not respond to treatment or fail to achieve durable responses. Histone deacetylase inhibitors (HDACi) have emerged as promising immunomodulatory agents, with the potential to sensitize tumors to ICIs. We investigated the immunomodulatory effects of entinostat, a class I HDACi, in combination with dual ICI (anti-PD-1 and anti-CTLA-4) as well as with T-cell receptor (TCR) engineered T cells in preclinical NSCLC models. Methods: We employed human NSCLC cell lines and the immunogenic KRASG12D/p53-mutant KPN1.1 murine NSCLC cell line. In vitro, we assessed entinostat-induced changes in MHC class I and PD-L1 expression. In addition, we evaluated the effects of entinostat on a KRASG12D-specific TCR. In vivo, therapeutic efficacy and immune modulation were assessed by transplanting KPN1.1 cells subcutaneously and orthotopically into immunocompetent mice, followed by treatment with dual ICI, with or without entinostat. Immune populations in the spleen and blood were subsequently analyzed. Results: In vitro, entinostat induced the upregulation of MHC-I and PD-L1 expression in both human and murine NSCLC cell lines. In addition, entinostat treatment significantly enhanced antigen-specific tumor recognition and killing by T cells engineered to express a KRASG12D-specific TCR. In vivo, the addition of entinostat to dual immune checkpoint inhibition showed an incremental trend toward improved tumor growth control. Notably, entinostat plus dual ICI enhanced systemic immune activation, increasing circulating and splenic T-cell populations and significantly expanding both antigen-specific and overall effector CD8⁺ T cells. Consistently, the ex vivo co-culture of splenocytes from KPN1.1-bearing mice with KPN1.1 tumor cells demonstrated enhanced CD8⁺ antigen-specific T-cell recognition. Conclusions: In human and murine NSCLC models, entinostat potentiates TCR- and ICI-mediated tumor recognition through tumor-intrinsic and systemic immune modulation. These effects were reflected by increased MHC-I expression, expansion of antigen-specific effector CD8⁺ T cells, and enhanced CD8⁺ T-cell tumor recognition. These findings support a further evaluation of entinostat as a strategy to improve immunotherapy efficacy in NSCLC. Full article

Background: Chimeric antigen receptor (CAR) T-cell therapy has transformed haematological-malignancy care, but its dermatologic safety profile remains incompletely characterised across products and indications. Methods: We analysed 8,431,841 deduplicated FDA Adverse Event Reporting System reports from 2016 Q3 to 2026 Q1. Seven approved CAR T-cell products were identified. The primary outcome was any dermatologic adverse event, defined using the MedDRA Skin and subcutaneous tissue disorders system organ class. Secondary outcomes included broad severe cutaneous adverse reactions, narrow Stevens-Johnson syndrome/toxic epidermal necrolysis, and 14 phenotype-specific categories. Multivariable models adjusted for demographics, polypharmacy, cancer, immune checkpoint inhibitor exposure, lymphodepleting chemotherapy and cytokine release syndrome. Additional sensitivity analyses evaluated HSCT/GVHD co-reporting proxies, infection and cytopenia/bleeding proxies, severe-event clinical characteristics, comparator robustness and multiplicity correction. Results: Dermatologic adverse events were identified in 996,654 reports, including 425 CAR-T-associated cases. CAR T-cell exposure was associated with reduced adjusted reporting odds for the primary outcome (adjusted odds ratio 0.13, 95% confidence interval 0.09–0.20) and broad severe cutaneous adverse reactions (0.35, 0.23–0.52). The primary SKIN_ANY reduced-reporting pattern was consistent across all-FAERS, haematological-malignancy and active haematology-oncology comparators. HSCT/GVHD proxy co-reporting was uncommon and did not materially alter estimates. Severe dermatologic reports frequently co-mentioned CRS and serious outcomes. The tisagenlecleucel vascular cutaneous signal was nominally significant but attenuated after excluding infection-attributable and cytopenia/bleeding-proxy reports. Conclusions: Within spontaneous reporting systems, CAR T-cell therapy showed reduced relative reporting of dermatologic adverse events across broad, phenotype-specific and product-level analyses. These results should be interpreted as differences in reporting behaviour, not as evidence of reduced true clinical incidence or lower patient-level risk. Early severe cutaneous reports frequently overlapped with cytokine release syndrome, while infection, cytopenia/bleeding proxies and supportive-care drugs were important alternative explanations for selected cutaneous signals. Full article