Search Results (70)

BST2 has emerged as a multifunctional molecule that bridges antiviral defense, membrane architecture, and tumor immunity. Originally characterized as an interferon-inducible restriction factor that tethers virions to the plasma membrane, BST2 is now recognized as an oncogenic driver and immunoregulatory hub in diverse malignancies. In cancer, BST2 expression is frequently upregulated through promoter hypomethylation and transcriptional activation. Functionally, BST2 promotes proliferation, epithelial–mesenchymal transition, anoikis resistance, and chemoresistance, whereas its loss sensitizes tumor cells to proteotoxic and metabolic stresses. Beyond tumor cells, BST2 modulates the tumor microenvironment by promoting M2 macrophage infiltration, dendritic cell exhaustion, and natural killer (NK)-cell resistance, thereby contributing to immune evasion. Elevated BST2 expression correlates with poor prognosis in glioblastoma, breast, nasopharyngeal, and pancreatic cancers, and it serves as a circulating biomarker within small extracellular vesicles. In conclusion, BST2 is a dual-function molecule that integrates oncogenic signaling and immune regulation, making it an attractive diagnostic and therapeutic target for hematological and solid tumors. Full article

We describe RNA-Seq analyses conducted on nasopharyngeal swabs collected from 37 patients admitted to an Australian intensive care unit from October 2022 to August 2023. During this time, the dominant omicron sublineage infections broadly progressed from BA.5 to BA.2-like, to XBB-like, then XBC, consistent with global trends. Viral load and patient metadata correlations indicated this cohort was broadly representative of severe COVID-19 patients. Human gene expression analyses were complicated by the large range (>5 log) and variability in viral reads. Nevertheless, the comparison of XBC and BA.5 samples that had comparable viral read counts, revealed differentially expressed genes and a cellular deconvolution signature that indicated increased targeting of ciliated epithelial cells by XBC. To obtain more evidence for increased targeting of ciliated epithelial cells by the later omicron sublineage viruses, a series of mouse strains were infected with a BA.5 or a XBB isolate. Increased infection of the nasal turbinates and ciliated epithelial cells by XBB was demonstrated by viral titrations and immunohistochemistry, respectively. Compared with previous lineages, the omicron lineage showed increased targeting of ciliated epithelia in the upper respiratory tract, with the data presented herein suggesting this trend continued for the omicron sublineages. Full article

The undifferentiated nasopharyngeal cancer (NPC) is a multifactorial disease mainly due to Epstein-Barr Virus (EBV) infection. The transmembrane tyrosine kinase ‘EphA2’ and the protease ‘Furin’ are implicated in the EBV entry into epithelial cells and other physiological processes. To gain insights into the association of single-nucleotide polymorphisms (SNPs) rs4702 and rs6603883 (FURIN and EPHA2 genes, respectively) with the risk and prognosis of the NPC, the genotypes of 471 individuals (228 cases and 243 controls) were assessed alongside risk cofactors (sex, tobacco, alcohol, occupation, and recurrent Ear, Nose and Throat infections) and prognosis cofactors (Tumor stage, local invasion, lymph node involvement, and metastasis) using multivariable logistic regression. We found that only the rs4702 AG/GG genotypes were statistically significantly associated with a reduced risk of cancer, both in the overall population and in men (approximately 50% reduction). The rs4702 GG genotype was also associated with a low frequency of local tumor invasion in the whole population (OR = 0.382, p = 0.017, co-dominant model, and OR = 0.409, p = 0.02, recessive model), but heterozygous women were associated with a higher lymph node involvement (OR = 3.53, p = 0.031, co-dominant model, and OR = 3.62, p = 0.02, overdominant model). The rs6603883 GG genotype was associated, in the dominant model, with distant metastasis in the whole population (OR = 2.5, p = 0.024), with advanced clinical stage in men (OR = 2.22, p = 0.034), and with advanced clinical stage and distant metastasis in patients under 49 years (OR = 3.13, p = 0.009, and OR = 5.15, p = 0.011, respectively). Additionally, men having the rs6603883 GA genotype were associated with lymph node invasion (OR = 2.22, p = 0.027, overdominant model). Our study is the first to demonstrate that FURIN and EPHA2 germline gene polymorphisms are associated with NPC risk (for rs4702) and prognosis (for both rs4702 and rs6603883), with sex-specific differences. These results need to be replicated and further investigated in other populations. Full article

Chronic nasopharyngeal and otic disorders in children represent a significant clinical challenge due to their multifactorial etiology, variable presentation, and frequent resistance to standard therapies. Although often approached from a symptomatic or anatomical perspective, these conditions are deeply rooted in histological and molecular alterations that sustain inflammation, impair mucosal function, and promote recurrence. This narrative review synthesizes the current knowledge on the normal histology of the nasopharynx, Eustachian tube, and middle ear, and explores key pathophysiological mechanisms, including epithelial remodeling, immune cell infiltration, cytokine imbalance, and tissue fibrosis. Special emphasis is placed on the role of immunohistochemistry in defining inflammatory phenotypes, barrier dysfunction, and remodeling pathways. The presence of biofilm, epithelial plasticity, and dysregulated cytokine signaling are also discussed as contributors to disease chronicity. These findings have direct implications for diagnosis, therapeutic stratification, and postoperative monitoring. By integrating histological, immunological, and molecular data, clinicians can better characterize disease subtypes, anticipate treatment outcomes, and move toward a more personalized and biologically informed model of pediatric ENT care. Full article

Introduction: The limited value of TNM staging in locally advanced (LA) nasopharyngeal carcinoma (NPC), defined as stage III or IV NPC, highlights the need for prognostic markers. Here, we aimed to evaluate the ability of the cancer stem cell markers, BMI1, ALDH1, CD44, and CD24, and the epithelial–mesenchymal transition marker, vimentin, as novel prognostic markers in LA-NPC. Methods: A cohort of 83 patients with LA-NPC, previously recruited for another trial with a different goal, was used. The marker expression in tissue sections was evaluated using immunohistochemistry, and the association of expression with survival outcomes was analyzed using the Kaplan–Meier method and Cox regression analysis. Results: The expression of BMI1 and ALDH1 was not associated with survival. The tumoral expression of CD24, CD44, and vimentin was significantly associated with disease-free survival (DFS), whereas only the expression of CD24 was also significantly associated with overall survival (OS). Indeed, CD24 expression emerged as an independent prognostic factor as it was associated with survival in univariate and multivariate Cox regression analysis. Interestingly, combining the status of CD24 expression in tumor cells with the density of CD3⁺ tumor-infiltrating lymphocytes (TIL), a microenvironment/immune-related marker, identified a high-risk subgroup with the worst DFS and OS. Conclusions: These results suggest the utility of combining tumoral CD24 expression and the CD3⁺ TIL density as a prognostic factor in LA-NPC, with potential application in disease management and future trial design. Our findings also highlight the potential of combining immune- and cancer stem cell-related factors in personalized treatment strategies for cancer. Full article

Respiratory syncytial virus (RSV) is the leading cause of respiratory infections in children. Extracellular vesicles (EVs), released by airway epithelial cells, contain proteins and different families of non-coding RNAs (EV cargo) that can modulate the responses of target cells to viral infection. Nasal mucosa is a primary site of viral entry and the source of EVs present in the upper airway secretions. In this study we characterized proteins, including inflammatory mediators and cytokines, and the piwi-interacting RNA (piRNAs) cargo of EVs isolated from pediatric human nose organoids (HNO) and nasopharyngeal secretions (NPS) positive for RSV. Using Proximity Extension Assay (PEA) and Luminex multi-target arrays, we found significant enrichment in several chemokines and other mediators/biomarkers, including CCL2, CCL20, CXCL5, CX3CL1, CXCL6, MMP-1, MMP-10, uPA, Flt3L, ARNT and CD40 in EVs secreted by RSV-infected HNO compared to control mock HNO. Analysis of NPS samples from RSV infected children revealed that CCL3, CCL20, CXCL8, uPA, VEGFA, were concentrated in the NPS-EV fraction. LC-MS/MS and Gene Ontology indicated that RSV positive NPS-EVs originate from different cellular sources, with the most abundant proteins from neutrophils and epithelial cells. A total of 490 piRNAs were detected by NGS sequencing of small RNA libraries obtained from NPS-EVs, which has not been reported prior to this study. Identification of inflammatory mediators and small non-coding RNAs which are compartmentalized in EVs contributes to understanding mechanisms of virus-mediated pathogenesis in RSV infections. Full article

Respiratory syncytial virus (RSV) is the leading cause of lower respiratory tract viral infection in infants and causes around 60,000 in-hospital deaths annually. Emerging evidence suggests that RSV induces metabolic changes in host cells to support viral replication, presenting a potential target for therapeutic intervention. To investigate RSV-driven metabolic changes in situ, we combined positron emission tomography (PET), live-cell bioenergetics, and metabolomic profiling in the upper and lower airways of children. PET imaging revealed persistent, hyper-glycolytic regions in the lungs of RSV-infected children. Bioenergetic analysis of freshly collected nasopharyngeal aspirates from infants showed live upper respiratory cells (URCs) infected with RSV in situ exhibited significantly higher levels of glycolysis, glycolytic capacity, glycolytic reserves, and mitochondrial respiration than uninfected controls. Metabolomic analysis of nasopharyngeal fluids from these patients revealed distinct metabolic signatures, including increased citrate and malate, and decreases in taurine. In vitro infection of pediatric nasopharynx tissue-derived multicellular epithelial cultures (TEpiCs) and bronchial epithelial cells further confirmed RSV-induced increases in glycolysis. Together, these findings demonstrate that RSV infection induces hypermetabolism in both upper and lower primary airways in situ, supporting the potential of host-targeted metabolic interventions as a therapeutic strategy—particularly in vulnerable populations such as infants for whom vaccines are not currently available. Full article

Background: Epstein–Barr virus (EBV) is involved in the development of lymphomas, nasopharyngeal carcinomas (NPC), and a subgroup of gastric carcinomas (GC), and has also been detected in lung carcinomas, even though the role of the virus in this malignancy has not yet been established. BamH1-A Rightward Frame 1 (BARF1), a suggested exclusive epithelial EBV oncoprotein, is detected in both EBV-associated GCs (EBVaGC) and NPC. The expression and role of BARF1 in lung cancer is unknown. Methods: A total of 158 lung carcinomas including 80 adenocarcinomas (AdCs) and 78 squamous cell carcinomas (SQCs) from Chilean patients were analyzed for EBV presence via polymerase chain reaction (PCR), Immunohistochemistry (IHC), or chromogenic in situ hybridization (CISH). The expression of BARF1 was evaluated using Reverse Transcription Real-Time PCR (RT-qPCR). Additionally, A549 and BEAS-2B lung epithelial cells were transfected with a construct for ectopic BARF1 expression. Cell proliferation, migration, invasion, and epithelial–mesenchymal transition (EMT) were evaluated. Results: We found that EBV was present in 37 out of 158 (23%) lung carcinomas using PCR. Considering EBV-positive specimens using PCR, IHC for Epstein–Barr nuclear antigen 1 (EBNA1) detected EBV in 24 out of 30 (80%) cases, while EBERs were detected using CISH in 13 out of 16 (81%) cases. Overall, 13 out of 158 (8%) lung carcinomas were shown to be EBV-positive using PCR/IHC/CISH. BARF1 transcripts were detected in 6 out of 13 (46%) EBV-positive lung carcinomas using RT qPCR. Finally, lung cells ectopically expressing BARF1 showed increased migration, invasion, and EMT. Conclusions. EBV is frequently found in lung carcinomas from Chile with the expression of BARF1 in a significant subset of cases, suggesting that this viral protein may be involved in EBV-associated lung cancer progression. Full article

Epstein–Barr virus (EBV), a member of the γ-herpesvirus family, is one of the most prevalent and persistent human viruses, infecting up to 90% of the adult population globally. EBV’s life cycle includes primary infection, latency, and lytic reactivation, with the virus primarily infecting B cells and epithelial cells. This virus has evolved sophisticated strategies to evade both innate and adaptive immune responses, thereby maintaining a lifelong presence within the host. This persistence is facilitated by the expression of latent genes such as EBV nuclear antigens (EBNAs) and latent membrane proteins (LMPs), which play crucial roles in viral latency and oncogenesis. In addition to their well-known roles in several types of cancer, including nasopharyngeal carcinoma and B-cell lymphomas, recent studies have identified the pathogenic roles of EBV in autoimmune diseases such as multiple sclerosis, rheumatoid arthritis, and systemic lupus erythematosus. This review highlights the intricate interactions between EBV and the host immune system, underscoring the need for further research to develop effective therapeutic and preventive strategies against EBV-associated diseases. Full article

Head and neck cancers (HNCs) constitute a wide range of malignancies originating from the epithelial lining of the upper aerodigestive tract, including the oral cavity, pharynx, larynx, nasal cavity, paranasal sinuses, and salivary glands. Although lymphomas affecting this region are not conventionally classified as HNCs, they may occur in lymph nodes or mucosa-associated lymphoid tissues within the head and neck. Oncogenic viruses play a crucial role in HNC onset. Human papillomavirus (HPV) is extensively studied for its association with oropharyngeal cancers; nevertheless, other oncogenic viruses also contribute to HNC development. This review provides an overview of the epidemiology, pathogenesis, and advancements in detection methods of oncogenic viruses associated with HNCs, recognizing HPV’s well-established role while exploring additional viral connections. Notably, Epstein–Barr virus is linked to nasopharyngeal carcinoma and lymphomas. Human herpesvirus 8 is implicated in Kaposi’s sarcoma, and Merkel cell polyomavirus is associated with subsets of HNCs. Additionally, hepatitis viruses are examined for their potential association with HNCs. Understanding the viral contributions in the head and neck area is critical for refining therapeutic approaches. This review underlines the interaction between viruses and malignancies in this region, highlighting the necessity for ongoing research to elucidate additional mechanisms and enhance clinical outcomes. Full article

Chitosan, a natural polysaccharide derived from chitin, possesses biocompatibility, biodegradability, and mucoadhesive characteristics, making it an attractive material for the delivery of mRNA payloads to the nasal mucosa and promoting their uptake by target cells such as epithelial and immune cells (e.g., dendritic cells and macrophages). In this project, we aimed at developing novel lipid-based nanoformulations for mRNA delivery to counteract the pandemic caused by SARS-CoV-2 virus. The formulations achieved a mRNA encapsulation efficiency of ~80.2% with chitosan-lipid nanoparticles, as measured by the RiboGreen assay. Furthermore, the evaluation of SARS-CoV-2 Spike (S) receptor-binding domain (RBD) expression via ELISA for our vaccine formulations showed transfection levels in human embryonic kidney cells (HEK 293), lung carcinoma cells (A549), and dendritic cells (DC 2.4) equal to 9.9 ± 0.1 ng/mL (174.7 ± 1.1 fold change from untreated cells (UT)), 7.0 ± 0.2 ng/mL (128.1 ± 4.9 fold change from UT), and 0.9 ± 0.0 ng/mL (18.0 ± 0.1 fold change from UT), respectively. Our most promising vaccine formulation was also demonstrated to be amenable to lyophilization with minimal degradation of loaded mRNA, paving the way towards a more accessible and stable vaccine. Preliminary in vivo studies in mice were performed to assess the systemic and local immune responses. Nasal bronchoalveolar lavage fluid (BALF) wash showed that utilizing the optimized formulation resulted in local antibody concentrations and did not trigger any systemic antibody response. However, if further improved and developed, it could potentially contribute to the management of COVID-19 through nasopharyngeal immunization strategies. Full article

Nasopharyngeal carcinoma is one of the most common malignant tumors in the head and neck region. The carcinogenesis is a complex process stimulated by many factors. Although the etiological factors and pathogenic mechanisms are not elucidated, the genetic susceptibility, environmental factors, and association with latent infection with Epstein–Barr Virus play an important role. The aim of this study was to present the main clinical and epidemiological data, as well as the morphological aspects and the immunohistochemical profile, of patients with nasopharyngeal carcinoma diagnosed in western Romania. The study was retrospective and included 36 nasopharyngeal carcinomas. The histopathological diagnosis was completed using immunohistochemical reactions for the following antibodies: p63, p53 and p16 protein, cytokeratins (CK) AE1/AE3, CK5, CK7, CK20 and 34βE12, epithelial membrane antigen (EMA), Epstein–Barr virus (EBV), leukocyte common antigen (LCA), CD20, CD4, CD8, CD68, CD117, and CD1a. The squamous malignant component of nasopharyngeal carcinoma presented with positivity for cytokeratins AE1/AE3, CK5, 34βE12, and p63. Undifferentiated nasopharyngeal carcinoma was positive for EMA in 67% of cases, and 28% of cases showed an immunoreaction for CD117 in the malignant epithelial component. Also, the p53 protein was positive in all the cases. One case of undifferentiated nasopharyngeal carcinoma was p16-positive, and two cases were positive for EBV. A peri- and intratumor cellular infiltrate rich in lymphocytes, with a predominance of CD20-positive B lymphocytes, interspersed with T lymphocytes, was observed. The T cells were CD4- and CD8-positive, predominantly intratumoral, and the CD4:CD8 ratio was 1:1 for 75% of the undifferentiated subtype and 89% for differentiated non-keratinized squamous cell carcinoma. All subtypes of nasopharyngeal carcinoma presented with an inflammatory infiltrate with numerous plasma cells, eosinophils, and dendritic cells, presenting as antigen CD1a- and CD68-positive, as well as in CD117-positive mast cells. Full article

Nasopharyngeal carcinoma (NPC) is an epithelial malignancy situated in the posterolateral nasopharynx. NPC poses grave concerns in Southeast Asia due to its late diagnosis. Together with resistance to standard treatment combining chemo- and radiotherapy, NPC presents high metastatic rates and common recurrence. Despite advancements in immune-checkpoint inhibitors (ICIs) and cytotoxic-T-lymphocytes (CTLs)-based cellular therapy, the exhaustive T cell profile and other signs of immunosuppression within the NPC tumour microenvironment (TME) remain as concerns to immunotherapy response. Exosomes, extracellular vesicles of 30–150 nm in diameter, are increasingly studied and linked to tumourigenesis in oncology. These bilipid-membrane-bound vesicles are packaged with a variety of signalling molecules, mediating cell–cell communications. Within the TME, exosomes can originate from tumour, immune, or stromal cells. Although there are studies on tumour-derived exosomes (TEX) in NPC and their effects on tumour processes like angiogenesis, metastasis, therapeutic resistance, there is a lack of research on their involvement in immune evasion. In this review, we aim to enhance the comprehension of how NPC TEX contribute to cellular immunosuppression. Furthermore, considering the detectability of TEX in bodily fluids, we will also discuss the potential development of TEX-related biomarkers for liquid biopsy in NPC as this could facilitate early diagnosis and prognostication of the disease. Full article

The embryonic development of neural crest cells and subsequent tissue differentiation are intricately regulated by specific transcription factors. Among these, SOX10, a member of the SOX gene family, stands out. Located on chromosome 22q13, the SOX10 gene encodes a transcription factor crucial for the differentiation, migration, and maintenance of tissues derived from neural crest cells. It plays a pivotal role in developing various tissues, including the central and peripheral nervous systems, melanocytes, chondrocytes, and odontoblasts. Mutations in SOX10 have been associated with congenital disorders such as Waardenburg–Shah Syndrome, PCWH syndrome, and Kallman syndrome, underscoring its clinical significance. Furthermore, SOX10 is implicated in neural and neuroectodermal tumors, such as melanoma, malignant peripheral nerve sheath tumors (MPNSTs), and schwannomas, influencing processes like proliferation, migration, and differentiation. In mesenchymal tumors, SOX10 expression serves as a valuable marker for distinguishing between different tumor types. Additionally, SOX10 has been identified in various epithelial neoplasms, including breast, ovarian, salivary gland, nasopharyngeal, and bladder cancers, presenting itself as a potential diagnostic and prognostic marker. However, despite these associations, further research is imperative to elucidate its precise role in these malignancies. Full article

The Epstein–Barr virus (EBV) is associated with various tumor types, including nasopharyngeal carcinoma and lymphoproliferative disorders. While much is known about EBV-related epithelial and lymphoid tumors, there is a paucity of knowledge concerning EBV-associated mesenchymal tumors. This review aims to provide a comprehensive overview of EBV-associated mesenchymal tumors, encompassing their clinical features, pathological characteristics, pathophysiology, prognostic factors, and current treatment approaches. Through an extensive literature search using the PubMed database, we were able to identify three distinct EBV-associated mesenchymal tumors: EBV-associated smooth muscle tumors, inflammatory pseudotumor-like follicular dendritic cell sarcomas, and EBV-associated osteosarcomas. Although this review extensively explored the different aspects of these mesenchymal tumors, our comprehension of the underlying pathophysiology in this context is still incomplete. Therefore, we hope that this review paper will not only serve as a valuable repository of information but also serve as a catalyst for prospective in vitro and in vivo research studies to bridge the existing knowledge gap surrounding pathophysiology, ultimately making an important contribution to shaping future therapeutic approaches. Full article