[This corrects the article DOI: 10.3389/fimmu.2026.1775221.].
BackgroundBispecific antibodies (BsAbs) have emerged as a promising strategy for solid tumor treatment, yet their comparative efficacy and safety versus other antitumor therapies remain unclear.Materials and methodsLiterature was systematically searched in PubMed, Embase, Cochrane Library, and Scopus from inception up to August 2026. American Society of Clinical Oncology (ASCO), European Society for Medical Oncology (ESMO) and clinicaltrials.gov were also checked. Progression-free survival (PFS), overall survival (OS), overall response rate (ORR), and adverse events (AEs) were used to assess efficacy and safety. Publication bias was assessed using funnel plots. Heterogeneity was evaluated using subgroup, meta-regression and sensitivity analyses. The protocol was preregistered in the International Prospective Register of Systematic Reviews (CRD420261359397).ResultsA total of 9 eligible studies involving 3,505 patients were included. Compared with other antitumor therapies, BsAbs demonstrated significant improvements in PFS (hazard ratio [HR]: 0.76, 95% confidence interval [CI]: 0.61-0.94, p=0.011) and OS (HR: 0.78, 95% CI: 0.63-0.95, p=0.016). ORR showed a borderline effect (Risk Ratio [RR]: 1.20, 95% CI: 1.00-1.44, p=0.046). Subgroup analyses suggested potential benefits in selected populations, particularly among patients treated with T-cell engaging BsAbs or tumor microenvironment/angiogenesis-modulating BsAbs, patients aged <65 years, and patients with non-small cell lung cancer (NSCLC). Regarding safety, renal and vascular toxicities, including proteinuria, peripheral edema, and hypertension, as well as immune-related toxicities such as cytokine release syndrome and rash, were more frequently observed in the BsAb group. Other increased adverse events included anemia, pain in extremity, decreased appetite, and vomiting.ConclusionBsAb-based regimens significantly improve PFS and OS compared with non-BsAb antitumor therapies in patients with solid tumors. Although the overall AE profile appeared manageable, renal and vascular toxicities and immune-related/inflammatory toxicities warrant particular attention.Systematic review registrationhttps://www.crd.york.ac.uk/PROSPERO/, identifier CRD420261359397.
The gut and liver form an anatomical and functional unit linked by the portal circulation, the biliary tract, lymphatic drainage, and neuroimmune pathways. In recent years, the classical gut-liver axis has expanded from a predominantly microbial and metabolic concept into a broader framework in which immune cells are viewed as central integrators of inter-organ signaling. In health, balanced microbial sensing, intact mucosal and vascular barriers, regulated bile acid signaling, and specialized tissue-resident immune programs preserve tolerance at both intestinal and hepatic interfaces. In disease, dysbiosis, barrier failure, altered bile acid pools, endogenous hepatotoxic metabolites, and aberrant immune-cell trafficking remodel the hepatic immune niche and drive steatohepatitis, alcohol-associated liver injury, cholangiopathy, cirrhosis, acute decompensation, and hepatocellular carcinoma. This review reframes the gut-liver axis as a gut-liver-immune axis and synthesizes current evidence on its structural basis, cellular architecture, molecular mediators, and disease-specific manifestations. We discuss the roles of macrophages, dendritic cells, neutrophils, innate-like T cells, natural killer cells, and adaptive T-cell subsets in translating gut-derived signals into hepatic inflammation, tissue repair, fibrosis, or tumor surveillance. We also highlight the bidirectional role of the liver in shaping intestinal immunity, particularly through bile acids and hepatobiliary-derived mediators. Finally, we examine current therapeutic strategies targeting the microbiota, mucosal barrier, bile acid signaling, and immune-cell trafficking, and we outline major conceptual and translational gaps that should guide the next generation of mechanistic and clinical studies.
Pemphigus vulgaris (PV) is a chronic autoimmune blistering disease characterized by intraepidermal flaccid blisters of the skin and mucous membranes. Although typically chronic and relapsing, rare fulminant variants have been described. We report a life-threatening case of PV in a previously healthy 55-year-old woman who developed a rapidly progressive, Stevens–Johnson syndrome/toxic epidermal necrolysis (SJS/TEN)-like phenotype with extensive epidermal detachment and mucocutaneous involvement. Histopathological analysis demonstrated suprabasal acantholysis, and direct immunofluorescence showed intercellular IgG and C3 deposition. Serology revealed markedly elevated anti–Desmoglein-1 (107.5 IU/mL) and modest anti–Desmoglein-3 titers (9.6 IU/mL). The clinical course was complicated by Cytomegalovirus reactivation, while malignancy screening remained negative. Treatment with rituximab and intravenous immunoglobulin led to rapid re-epithelialization and clinical stabilization. This case expands the clinical spectrum of PV and underscores diagnostic and therapeutic challenges posed by fulminant autoimmune blistering disease exhibiting overlapping features. As rat-bladder indirect immunofluorescence and extended plakin serology were not available, a paraneoplastic pemphigus (PNP)-spectrum disorder could not be formally excluded, although the clinical, histological, and serological picture strongly favored PV. We propose that markedly elevated anti-Dsg1 antibodies, complement activation, and CMV reactivation may each have contributed to this severe phenotype.
Combined Allergic Rhinitis and Asthma Syndrome (CARAS) in children is a chronic airway inflammatory disorder with a high prevalence in childhood. In recent years, a growing body of studies has identified a close association between fractional exhaled nitric oxide (FeNO) and nasal exhaled nitric oxide (nNO) and the pathogenesis of CARAS in children. By synthesizing relevant literature retrieved from the PubMed database (1985-2025), this article provides an in-depth analysis of the roles of the NO/cyclic guanosine monophosphate (cGMP) signaling pathway, nitrosative stress, and organelle injury in the pathogenesis of CARAS in children. Meanwhile, it reviews the potential clinical significance of exhaled nitric oxide as a non-invasive biomarker in supporting the diagnosis and therapeutic monitoring of CARAS in children, analyzes the latest research advances and existing controversies, and outlines future research directions, thereby providing a theoretical basis for the optimized clinical management of this disease.
Angiogenesis is a fundamental physiological process; however, its pathological dysregulation drives diseases such as solid tumors, wet age-related macular degeneration, and rheumatoid arthritis. Although clinically effective, conventional anti-angiogenic monoclonal antibodies are limited by poor tissue penetration, off-target toxicities, and susceptibility to compensatory resistance. This review systematically examines the structural advantages and engineering strategies of nanobodies (Nbs) targeting angiogenesis-related pathways. Advanced engineering approaches, such as AI-assisted humanization and multivalent assembly, effectively mitigate immunogenicity and extend serum half-life. Furthermore, multispecific designs can simultaneously block compensatory pathways to circumvent resistance. Moreover, preclinical studies indicate that integrating these molecules into site-specific nanobody-drug conjugates and targeted delivery vehicles may improve therapeutic precision and local drug accumulation; however, their long-term safety, manufacturability, and clinical benefit remain to be established. Functionalizing Nbs with radionuclides or fluorophores may enable the development of novel theranostic platforms that support real-time molecular imaging and image-guided surgery. In parallel, nanobody-based CAR-T (Nb-CAR-T) cells facilitate the targeted remodeling of the disease microenvironment. Ultimately, this review highlights the value of engineered Nbs as a highly programmable and transformative platform. By overcoming key limitations of conventional antibodies, engineered nanobodies open new avenues for precise, multi-dimensional interventions in solid tumors. Their potential in certain non-neoplastic angiogenic diseases is emerging but requires further validation.
BackgroundImmune signaling is tightly coupled to cellular metabolic state. Beyond supplying energy, metabolites can directly regulate immune responses by driving post-translational modifications of proteins and chromatin, shifting immunometabolism toward a model in which metabolic state encodes signaling outputs.FindingsProtein pyruvylation has recently emerged as a metabolite-responsive lysine modification linking glycolytic metabolism to both immune signaling and transcriptional regulation. Established examples, including histone lactylation and acylation marks linked to acetyl-CoA and crotonyl-CoA, illustrate how metabolite availability shapes chromatin state and transcriptional competence. A recent Cell study showed that high glucose-enhanced glycolysis and pyruvate kinase M2 activity promotes STAT1 pyruvylation at Lys201, thereby disrupting STAT1-STAT2 interaction and suppressing type I interferon signaling. Complementing this signaling-centered mechanism, a subsequent Nature Metabolism study systematically characterized a broader lysine pyruvylation landscape, identified histone and non-histone substrates, linked pyruvylation to glycolytic flux and pyruvyl-CoA metabolism, and implicated HAT1 and p300 as pyruvylation writers and SIRT3 as an eraser. Together, these findings expand pyruvylation from a single signaling event into an emerging metabolite-responsive regulatory system operating across protein signaling and chromatin-associated transcriptional control. In this review, we summarize the conceptual framework of metabolite-driven protein modifications, compare established marks, and discuss the remaining questions surrounding pyruvylation chemistry, enzyme and substrate specificity, reader mechanisms, compartmentalization, detection strategies, physiological relevance, and potential immunopharmacological implications.ConclusionsMetabolite-driven protein modifications represent an important regulatory layer linking metabolic rewiring to immune reprogramming. Elucidating the chemistry, regulatory machinery, substrate landscape, and physiological functions of pyruvylation will not only advance our understanding of immunometabolism but may also facilitate the development of metabolite-based biomarkers and therapeutic strategies for inflammatory and immune-related disease.
