Clinical and Experimental Medicine最新文献

Bones are not only mechanical structures but also highly active immunological organs. The bone marrow hosts hematopoietic, mesenchymal, and immune cells that continuously interact to coordinate bone remodeling, hematopoiesis, and systemic immune responses. Disruption of this osteoimmune network contributes to pathological conditions such as delayed fracture healing, osteoporosis, osteoarthritis, osteomyelitis, and other bone-destructive disorders. Mesenchymal stem/stromal cell-derived extracellular vesicles (MSC-EVs) have emerged as key paracrine mediators and promising therapeutic candidates within this system. In this review, we summarize current knowledge on the biogenesis, composition, and characterization of MSC-EVs, and then focus on how they modulate macrophages, neutrophils, T and B cells, natural killer (NK) cells, and other stromal populations in the bone microenvironment. We discuss preclinical evidence across major bone disorders, including fracture repair, osteoporosis, osteoarthritis, osteonecrosis, periodontitis, and osteomyelitis, emphasizing the immunomodulatory mechanisms involved (e.g., regulation of M1/M2 balance, Th17/Treg ratios, neutrophil extracellular traps, and NK cell activity). Finally, we outline translational progress, including early clinical studies, manufacturing and potency-assay challenges, and outstanding questions that must be addressed to integrate MSC-EVs into future therapeutic strategies for bone disease.

Dendritic cell (DC)-based vaccines have emerged as a promising and innovative approach in the immunotherapy of both solid tumors and hematologic malignancies. Owing to their unique capacity to present antigens and activate tumor-specific T cell responses, DC vaccines play a pivotal role in counteracting tumor immune evasion. Despite significant advances in vaccine development, several challenges - including the immunosuppressive tumor microenvironment, the complexities of designing optimal vaccines, and the difficulty of translating preclinical successes into consistent clinical outcomes - have limited their widespread effectiveness. This review highlights recent combinatory strategies aimed at enhancing the design and application of DC-based vaccines. These include the incorporation of neoantigens, tumor lysates, mRNA platforms, DC-tumor fusion constructs, and combination therapies involving immune checkpoint inhibitors and CAR-T cells. Furthermore, we examine the translational barriers that hinder the clinical implementation of these approaches and explore future directions for improving efficacy, safety, and personalization of DC vaccines. DC-based vaccines may be more effectively positioned to yield substantial and durable clinical advantages in standard oncology practice when these combinatorial strategies are integrated with rational clinical trial design, biomarker-informed patient selection, and rigorous compliance with manufacturing and regulatory standards. Ultimately, individualized and multifaceted strategies are expected to hold the greatest promise for improving therapeutic outcomes while minimizing adverse effects.

Autoimmune heparin-induced thrombocytopenia (aHIT) represents a severe variant of immune-mediated thrombocytopenias (IMTs) in which anti-platelet factor 4 (PF4) antibodies activate platelets independently of heparin, leading to both thrombosis and thrombocytopenia. Despite its clinical significance, aHIT remains poorly understood and lacks evidence-based immunomodulatory treatments. This narrative translational review integrates mechanistic and therapeutic insights from immune thrombocytopenia (ITP) and antiphospholipid syndrome (APS) to identify shared pathogenic pathways relevant to aHIT. Literature from 2015 to 2025 was analyzed across PubMed, Scopus, Web of Science, and ClinicalTrials.gov, focusing on FcγRIIa-Syk-BTK signaling and complement activation as central drivers of platelet activation and clearance. Preclinical and clinical data indicate that targeting these axes with Syk inhibitors (fostamatinib), BTK inhibitors (rilzabrutinib, zanubrutinib), and complement inhibitors (sutimlimab) can restore platelet counts and mitigate immune-driven thrombosis. These findings underscore the therapeutic potential of pathway-specific interventions in aHIT, highlighting the need for biomarker-guided, translational trials to validate their efficacy and safety. Bridging mechanistic evidence from ITP and APS provides a framework for precision immunotherapy in autoimmune HIT.

Among the most aggressive and resistant tumors of the central nervous system, glioblastoma (GBM) has a poor prognosis and few available treatments. Because of the tumor's infiltrative nature, immunosuppressive environment, and resistance mechanisms, traditional treatments such as radiotherapy, chemotherapy, and surgery offer only modest survival benefits. Bispecific T-cell engagers (TCEs) have shown promising preclinical and early clinical results, and immunotherapy has become a feasible strategy. TCEs efficiently promote antigen evasion and strong tumor lysis by directing cytotoxic T lymphocytes (CTLs) to tumor-associated antigens (TAA) such as the EGFRvIII ligands IL-13Rα2, Fn14, and NKG2D ligands (NKG2DLs). Although phase I clinical studies with AMG 596 have shown acceptable safety profiles and early indications of efficacy, preclinical mice have demonstrated prolonged longevity. However, challenges still exist, including the short half-life of TCEs molecules, limited T-cell infiltration, antigen heterogeneity, and the risk of neurotoxicity or cytokine release syndrome (CRS). Promising developments include novel approaches such as multivalent targeting, DNA-encoded or cell-delivered TCEs, and combinations with immune checkpoint inhibitors (ICIs) or CAR-T cells. With an emphasis on its integration into multimodal treatment approaches, this review highlights the safety, effectiveness, and potential uses of TCEs immunotherapy for gliomas.

Hepatitis B virus (HBV) infection is an important worldwide health issue and attribute to hepatocellular carcinoma (HCC) via direct oncogenic and indirect mechanisms. HBV reprograms the tumor microenvironment (TME) through immunosuppression, metabolic adaptation, and stromal remodel, allowing tumor promotion and immune evasion. This review examines HBV-induced TME changes, including epigenetic dysregulation, immune cell dysfunction, and fibrosis, as well as new therapeutic options including immune checkpoint blockade, adoptive cell therapy, and metabolic targeting to improve outcomes in HBV-related HCC.

Autoimmune gastritis (AIG) is a chronic disease characterized by specific immune damage to the gastric mucosa. Previous studies have mostly focused on the single immune pathway mainly mediated by T cells, but the synergistic role of humoral immunity in disease progression cannot be ignored. This article systematically reviews the immunological mechanism of AIG, and analyzes the inflammatory cascade immune mechanism centered on the self-attack of gastric parietal cells mediated by CD4⁺ T, with the pro-inflammatory roles of Th1/Th17 cells and defective suppressive function of Tregs as a supplement. This article emphasizes the imbalance between humoral and cellular immunity, including the pathogenic potential of autoantibodies and the synergistic role of T-B cells in promoting inflammation. Furthermore, while existing animal models (including genetic modification, lymphopenic, and non-lymphopenic models) can replicate features of human AIG such as gastric gland atrophy, they exhibit significant limitations regarding the mechanism of T-B cell collaboration, differences in cancer risk, and species specificity. This article systematically clarifies that AIG results from an imbalance between cellular and humoral immunity, providing a theoretical basis for targeted immunotherapy strategies.

Idiopathic pulmonary fibrosis (IPF) is a progressive and fatal lung disease, with unknown pathogenesis and no effective treatment. Identifying the key molecular of IPF in underlying mechanisms is critical for developing targeted therapies. Differentially expressed genes (DEGs) were identified based on GSE53845 data from the Gene Expression Omnibus (GEO) database and the Limma R package, followed by gene set enrichment analysis (GSEA). The key module genes selected by Weighted Gene Co-expression Network Analysis (WGCNA) were integrated with the DEGs. The hub genes were screened using three machine-learning algorithms, with further performance validated through Receiver Operating Characteristic (ROC) curves and nomogram models. In addition, validation was performed using external validation sets, in vitro experiments and human lung tissues. Enrichment analyses were conducted using GeneMANIA and GSEA. Branched chain amino acid transferase 2 (BCAT2) was identified as a central hub gene in IPF by intersecting key module genes with DEGs through WGCNA and machine learning methods. Experimental validation confirmed the significantly downregulation of BCAT2 in the lung tissues of IPF patients and in TGF-β1-treated alveolar epithelial cells (AECs). Moreover, upregulation of BCAT2 attenuated the expression of fibrosis markers in AECs exposed to TGF-β1. Ultimately, Co-expression analysis and GSEA indicated that BCAT2 is closely involved in several key signaling pathways. Collectively, our findings suggest that BCAT2 is a critical protective molecule in the pathogenesis of IPF and represents a potential therapeutic target for modulating the progression of pulmonary fibrosis.