Biomedical Journal最新文献

{"title":"Less is more: A single-dose, non-waiting neoadjuvant immunotherapy strategy for hepatocellular carcinoma","authors":"Kevin Kuan-Yu Chen,&nbsp;Tzu-Jung Lin,&nbsp;Te-Wei Su,&nbsp;Po-Da Chen,&nbsp;Ming-Chih Ho,&nbsp;Yao-Ming Wu,&nbsp;Ying-Chun Shen,&nbsp;Ann-Lii Cheng","doi":"10.1016/j.bj.2026.100994","DOIUrl":"10.1016/j.bj.2026.100994","url":null,"abstract":"<div><div>Neoadjuvant immune checkpoint inhibitors (ICIs) are increasingly being explored in multiple solid tumors, conventionally delivered as multi-cycle preoperative regimens or as part of perioperative strategies that include postoperative therapy. However, directly adopting these approaches presents distinct challenges in hepatocellular carcinoma (HCC). In the Asia-Pacific region, curative surgery remains feasible even for patients with a large tumor burden. These patients may derive the greatest benefit from neoadjuvant immunotherapy due to their high risk of recurrence, yet they also face the narrowest surgical window. Disease progression during prolonged neoadjuvant treatment period can easily hinder resectability. Additionally, intensive neoadjuvant treatment-related adverse events, especially hepatotoxicity, may delay surgery. A HCC-specific approach that prioritizes surgical feasibility while preserving benefit of immunotherapy is needed.</div><div>Recent pharmacodynamic and clinical evidence indicates that a single dose of programmed cell death-1 (PD-1) or its ligand (PD-L1) antibody can rapidly achieve near-complete receptor occupancy and early T-cell activation. Receptor occupancy can be sustained in the early postoperative period. This provides a strong scientific rationale for a <strong>single-dose, non-waiting neoadjuvant strategy</strong>, in which anti-PD-1 or anti-PD-L1 is administered shortly before surgery without delaying resection. Such an approach may allow early antitumor immune activation while minimizing treatment-related adverse events (TRAEs), preserving surgical feasibility and reducing logistical complexity. It may enhance acceptance among patients and surgeons. Future neoadjuvant trials in HCC should consider adopting this “less is more” paradigm to investigate whether abbreviated neoadjuvant immunotherapy can safely translate immunologic activation into meaningful clinical benefit, as measured by event-free survival.</div></div>","PeriodicalId":8934,"journal":{"name":"Biomedical Journal","volume":"49 4","pages":"Article 100994"},"PeriodicalIF":6.3,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147980437","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Molecular diagnostic platforms for mitochondrial diseases by conventional and long-read sequencing: Missing pieces","authors":"Kok-Siong Poon,&nbsp;Karen Mei-Ling Tan,&nbsp;Nor Azian Abdul Murad","doi":"10.1016/j.bj.2026.100992","DOIUrl":"10.1016/j.bj.2026.100992","url":null,"abstract":"","PeriodicalId":8934,"journal":{"name":"Biomedical Journal","volume":"49 4","pages":"Article 100992"},"PeriodicalIF":6.3,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148590028","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"More than just numbers: the expanding burden of non-communicable diseases","authors":"Aila Akosua Kattner","doi":"10.1016/j.bj.2026.101020","DOIUrl":"10.1016/j.bj.2026.101020","url":null,"abstract":"<div><div>Non-communicable diseases (NCDs) account for a major share of global mortality and disability, while their development and outcomes reflect interactions among behavioral, metabolic, socioeconomic, environmental, infectious, and non-modifiable factors. This issue of the Biomedical Journal highlights the breadth of contemporary research across NCD epidemiology, mechanisms, diagnosis, prevention, and treatment. A study from northern Peninsular Malaysia examines age- and sex-specific patterns in the burden of cardiovascular disease, respiratory disease, and diabetes, while a review considers the complex association between diabetes, vascular complications, and dementia. Further reviews address strategies to improve glioblastoma vaccines through enhanced antigen presentation and combination immunotherapy, as well as ultrasound-guided interventions for adhesive capsulitis, including stage-specific and structure-oriented approaches to pain relief and functional recovery. The original articles explore a single-dose, non-waiting neoadjuvant immunotherapy strategy for resectable hepatocellular carcinoma; emerging evidence on problematic ChatGPT use; genomic surveillance following an outbreak of carbapenem-resistant <em>Serratia marcescens</em>; the stage-specific role of miR-7974 in colorectal cancer; and the potential diagnostic relevance of DEC-1 in ischemic stroke. Other contributions investigate extracorporeal shockwave therapy as a means of reducing inflammation in experimental psoriasis and Fu's subcutaneous needling as a potential modulator of mitochondrial quality control and inflammatory signaling in a rat model of sciatica. A correspondence exchange on molecular diagnostic platforms for primary mitochondrial diseases discusses the validation, sensitivity, terminology, clinical practicality, and particular advantages of long-read nanopore sequencing.</div></div>","PeriodicalId":8934,"journal":{"name":"Biomedical Journal","volume":"49 4","pages":"Article 101020"},"PeriodicalIF":6.3,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148651613","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Problematic ChatGPT use: Manifestations, etiologies, and evaluation","authors":"Hui-Yuan Liao,&nbsp;Chih-Hung Ko,&nbsp;Cheng-Fang Yen","doi":"10.1016/j.bj.2026.100998","DOIUrl":"10.1016/j.bj.2026.100998","url":null,"abstract":"<div><h3>Background</h3><div>ChatGPT has rapidly permeated various domains, including education, industry, creativity, and daily life. While offering efficiency and emotional engagement, excessive reliance may lead to problematic use with adverse effects on mental health, cognition, and social functioning. This review synthesizes current evidence on manifestations, etiologies, assessment, and neurophysiological correlates of problematic ChatGPT use.</div></div><div><h3>Material and methods</h3><div>A narrative review of empirical studies, psychometric developments, theoretical models, and preliminary electroencephalogram findings was conducted, with cross-cultural comparisons across Taiwan, Turkey, China, Korea, Singapore, and the United States.</div></div><div><h3>Results</h3><div>Problematic ChatGPT use is prevalent among young adults and associated with depression, stress, impaired self-control, and functional difficulties. Psychometric tools such as the Problematic ChatGPT Use Scale, Conversational AI Dependence Scale, and Generative AI Dependency Scale provide initial frameworks but require further validation. Theoretical models (Interaction of Person–Affect–Cognition–Execution model, compensatory Internet use, dual-system theory) have been used to explain the roles of emotional regulation deficits, cognitive biases, and intuitive processing for the development of problematic ChatGPT use. Preliminary electroencephalogram studies suggest altered functional connectivity, paralleling digital addiction patterns.</div></div><div><h3>Conclusions</h3><div>Problematic ChatGPT use involves psychological, behavioral, and neurobiological mechanisms. Future research should strengthen psychometric validation, expand electroencephalogram investigations, and evaluate interventions such as digital literacy education, behavioral self-regulation, cognitive-behavioral therapy, and neurofeedback to promote healthier AI engagement.</div></div>","PeriodicalId":8934,"journal":{"name":"Biomedical Journal","volume":"49 4","pages":"Article 100998"},"PeriodicalIF":6.3,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148148350","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Functional dynamic modulation of colorectal cancer initiation and metastatic capacity by a novel MiR-7974 regulatory axis","authors":"Yu-Hao Liu,&nbsp;Yi-Tung Chen,&nbsp;Yu-Chang Chen,&nbsp;En Chin,&nbsp;Ying-Yu Lai,&nbsp;Chung-Pei Ma,&nbsp;Ian Yi-Feng Chang,&nbsp;Bertrand Chin-Ming Tan,&nbsp;Pei-Ting Hsu,&nbsp;Yi-Hsuan Lai,&nbsp;Wen-Sy Tsai,&nbsp;Chia-Yu Yang,&nbsp;Jau-Song Yu,&nbsp;Hung-Chih Hsu,&nbsp;Hsuan Liu","doi":"10.1016/j.bj.2025.100934","DOIUrl":"10.1016/j.bj.2025.100934","url":null,"abstract":"<div><h3>Background</h3><div>Colorectal cancer (CRC) is one of the most prevalently diagnosed malignancies. Frequent metastasis and recurrence render treatments ineffective. The accumulation of omics data has helped develop a comprehensive functional regulatory network underlying tumorigenesis, causing significant breakthroughs in cancer therapy.</div></div><div><h3>Methods</h3><div>Systematic transcriptomic analysis of CRC tissues and matched normal samples identified miR-7974 as a novel miRNA with distinct expression pattern in CRC. Independent RT-qPCR assays further validated its tumor-biased expression. To investigate the role of miR-7974 in tumor progression, a series of cell-based assays and xenograft models were conducted. Additionally, RNA sequencing, reporter assays, and functional rescue experiments were performed to delineate the downstream regulatory network, with specific focuses on the miR-7974/CDKN1A and miR-7974/MYO1E axes involved in tumor growth and metastasis.</div></div><div><h3>Results</h3><div>MiR-7974 demonstrated high expression in early CRC but decreased abundance in later stages. We uncover that miR-7974 augments cancer growth by mitigating the expression of the cell cycle regulator, CDKN1A, through in vitro assays. Concurrently, miR-7974 reduces cellular migration and invasion by targeting MYO1E. In-depth transcriptomic investigations revealed miR-7974's role in repressing the epithelial-to-mesenchymal transition (EMT) in CRC cells, thereby maintaining the tumor in a highly proliferative epithelial state. This result is congruent with miR-7974's pronounced expression in early-stage CRC and its attenuation in advanced, metastatic stages. Such dynamic changes in expression patterns elucidate miR-7974's prognostic significance. Despite its abundant expression in CRC tissues, patients with heightened miR-7974 levels achieved more favorable survival outcomes.</div></div><div><h3>Conclusions</h3><div>Our findings demonstrate that miR-7974 regulates EMT plasticity, promoting a rapidly proliferating epithelial phenotype while reducing metastatic potential in CRC. Dynamic miR-7974 expression, coupled with its associated target gene regulation, provides the mechanistic foundation for understanding the acquisition of metastatic potential. This emphasizes the functional effect of miR-7974 on CRC growth and provides a deeper understanding of miRNome dynamics during cancer development.</div></div>","PeriodicalId":8934,"journal":{"name":"Biomedical Journal","volume":"49 4","pages":"Article 100934"},"PeriodicalIF":6.3,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145647272","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"HIF-1 and DEC-1 levels in acute ischaemic stroke patients: Could DEC-1 be a new biomarker in stroke?","authors":"Filiz DEMİRDÖĞEN,&nbsp;Nuray BİLGE,&nbsp;Alper Eren","doi":"10.1016/j.bj.2025.100928","DOIUrl":"10.1016/j.bj.2025.100928","url":null,"abstract":"<div><h3>Background/objectives</h3><div>Although the underlying cause of ischemic stroke is vascular occlusion, the post-stroke pathophysiology remains unclear. Therefore, numerous biomarkers have been investigated for both diagnostic and prognostic purposes. In our study, the diagnostic value of the parameters NLR, PLR, RDW-CV, RDW-SD, HIF-1, and DEC-1 was comprehensively evaluated.</div></div><div><h3>Methods</h3><div>NLR, Blood samples from patients with ischemic stroke and healthy controls were analyzed for NLR, PLR, RDW-CV, RDW-SD, HIF-1, and DEC-1 levels. Demographic and clinical characteristics of both patient and control groups were recorded. The relationship between HIF-DEC measurements and laboratory parameters was subsequently assessed. For statistical analysis, the Mann-Whitney <em>U</em> test was used for comparisons between groups, and the Chi-Square test was applied for categorical variables.</div></div><div><h3>Results</h3><div>RDW-SD values were found to be higher in patients diagnosed with cerebrovascular accident (CVA) while DEC levels were lower in the stroke group. Although no significant correlation was observed between HIF levels and other parameters in either the CVA or control groups, there was a weak inverse correlation found between DEC and NLR (r: 0.258), and between DEC and RDW-CV (r: 0.268), and a weak linear correlation between DEC and RDW (r:0.319) in the whole group. No significant correlations were found between DEC and other measurements within either the control or CVA groups individually.</div></div><div><h3>Conclusions</h3><div>Our study may indicate that pathways increasing the levels of DEC-1, which acts on the PI3K/Akt pathway, could lead the development of new therapeutic strategies for ischemic stroke.</div></div>","PeriodicalId":8934,"journal":{"name":"Biomedical Journal","volume":"49 4","pages":"Article 100928"},"PeriodicalIF":6.3,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145430353","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Extracorporeal shockwave therapy ameliorates skin inflammation of imiquimod-induced psoriasis in mice","authors":"Shang-Hung Lin,&nbsp;Po-Sheng Cheng,&nbsp;Chang-Chun Hsiao,&nbsp;Chih-Hung Lee","doi":"10.1016/j.bj.2025.100930","DOIUrl":"10.1016/j.bj.2025.100930","url":null,"abstract":"<div><h3>Background</h3><div>Psoriasis is a chronic inflammatory disease characterized by abnormal keratinocyte proliferation and dermal inflammation. TNF-α and IL-17/23 play significant roles in the pathophysiology of psoriasis. The immunomodulatory effect of extracorporeal shockwave therapy (ESWT) has been widely applied in the treatment of chronic inflammatory disorders.</div></div><div><h3>Objective</h3><div>This study aimed to investigate the effect of ESWT on imiquimod (IMQ)-induced psoriatic lesions and the mechanisms by which ESWT affects macrophages and T cell subsets.</div></div><div><h3>Material and methods</h3><div>Five groups of mouse models were included: wild type (WT) mice without treatment, mice receiving ESWT alone, mice treated with IMQ alone, mice treated with IMQ and ESWT (n = 6), and mice treated with IMQ and adalimumab (anti- TNF-α). We measured epidermal thickness, inflammatory cell infiltration, and the levels of inflammatory cytokines in the skin.</div></div><div><h3>Results</h3><div>The increase in epidermal thickness caused by IMQ was substantially reduced by ESWT or adalimumab. In parallel, the increased number of IL17⁺ cells, along with the increased IL-23 and TNF-α induced by IMQ, decreased significantly after ESWT or adalimumab treatment. However, the IMQ-induced increase in the number of M1 and M2 macrophages was reduced selectively by ESWT, but not by adalimumab. Moreover, in vitro experiments revealed that ESWT decreased TNF-α production by M1 macrophages but increased IL-10 production by M2 macrophages.</div></div><div><h3>Conclusions</h3><div>ESWT significantly reduced epidermal thickness, macrophage and IL-17⁺ cell infiltration, and the expression of IL-23 and TNF-α in IMQ-induced psoriasis mice. These findings suggest that ESWT may ameliorate psoriatic skin lesions by modulating macrophage activity and IL-17⁺ cell–mediated inflammation.</div></div>","PeriodicalId":8934,"journal":{"name":"Biomedical Journal","volume":"49 4","pages":"Article 100930"},"PeriodicalIF":6.3,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13452956/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145501693","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ultrasound-guided intervention in adhesive capsulitis: A comprehensive review of therapeutic strategies","authors":"Wei-Ting Wu,&nbsp;Ke-Vin Chang,&nbsp;Po-Yin Shen,&nbsp;Levent Özçakar","doi":"10.1016/j.bj.2026.101001","DOIUrl":"10.1016/j.bj.2026.101001","url":null,"abstract":"<div><div>Adhesive capsulitis is a painful and disabling shoulder condition characterized by progressive synovial inflammation, capsular fibrosis, and global restriction of motion. Conventional treatment strategies, including physical therapy and landmark-guided intra-articular corticosteroid injection, often yield variable outcomes. Ultrasound-guided interventions have emerged as a precision-based therapeutic approach, enabling real-time visualization of pathological structures, accurate needle placement, and dynamic assessment of capsular mechanics. This narrative review summarizes current evidence on ultrasound-guided corticosteroid injection, hydrodilatation, coracohumeral ligament–targeted procedures, suprascapular nerve block, and silent manipulation under cervical nerve root block. Across studies; injection target, injectate composition, and mechanical distension strategy appear to influence short-term pain relief and functional improvement. Rotator interval–targeted injections and coracohumeral ligament release specifically address anterior capsular contracture and loss of external rotation. Hydrodilatation provides mechanical capsular expansion, although superiority over corticosteroid injection alone remains inconsistent. Suprascapular nerve block primarily facilitates early analgesia to support rehabilitation, whereas silent manipulation restores mobility through structured capsular release under ultrasound-guided anesthesia. Collectively, contemporary evidence supports a shift from uniform application of technique toward stage-specific, structure-oriented, and pathology-driven management. Integration of dynamic ultrasound assessment into treatment planning may further refine patient selection and optimize long-term functional recovery. Future investigations should focus on long-term durability, optimal injectate parameters, and individualized intervention algorithms.</div></div>","PeriodicalId":8934,"journal":{"name":"Biomedical Journal","volume":"49 4","pages":"Article 101001"},"PeriodicalIF":6.3,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148175185","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The hidden link between diabetes and dementia: Findings from recent epidemiological studies","authors":"Chin-Hsiao Tseng","doi":"10.1016/j.bj.2026.100985","DOIUrl":"10.1016/j.bj.2026.100985","url":null,"abstract":"<div><div>Recent epidemiological studies investigating the link between diabetes mellitus and dementia or Alzheimer's disease are narratively reviewed. Diabetes mellitus is associated with a significantly higher risk of dementia by 56%, more predominant for vascular dementia than Alzheimer's disease and tau pathology is more remarkable than amyloid <em>β</em> deposition. The increased risk is related to the burden of microvascular and macrovascular diseases in a dose-response pattern; and a threshold effect between glycemic control and dementia risk is observed. A treatment target of hemoglobin A1c &lt; 7% may be optimal for reducing the risk of dementia but hypoglycemia should be avoided. Antidiabetic drugs such as metformin, pioglitazone, sodium-glucose co-transporter 2 inhibitors and glucagon-like peptide 1 receptor agonists may show beneficial effects on dementia in observational studies. In a Taiwanese cohort study acarbose is also associated with a lower risk of dementia in female diabetes patients. When considering the repurposing of antidiabetic drugs in the treatment of patients with Alzheimer's disease, low-dose insulin detemir shows a promising effect in a network meta-analysis. A phase 3 clinical trial (MET-FINGER) is being conducted to investigate whether metformin plus lifestyle intervention can be effective in the prevention of Alzheimer's disease. Hyperuricemia, though considered a potential component of metabolic syndrome, seems to be associated with a lower risk of dementia. Sex hormones play some roles in cognitive function and females present a higher risk of dementia than males. However, additional studies are required to explore the impacts of sex and sex hormones on the development of dementia and Alzheimer's disease.</div></div>","PeriodicalId":8934,"journal":{"name":"Biomedical Journal","volume":"49 4","pages":"Article 100985"},"PeriodicalIF":6.3,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13452960/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147760933","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"New concepts for glioblastoma vaccine immunotherapy","authors":"Mariam Shallak,&nbsp;Amruth K.B. Shaik,&nbsp;Andrea Gatta,&nbsp;Mattia Volpi,&nbsp;Roberto S. Accolla,&nbsp;Greta Forlani","doi":"10.1016/j.bj.2026.100974","DOIUrl":"10.1016/j.bj.2026.100974","url":null,"abstract":"<div><h3>Background</h3><div>Glioblastoma remains one of the most lethal malignancies, characterized by rapid recurrence, profound intratumoral heterogeneity, and a highly immunosuppressive microenvironment.</div><div>Among immunotherapeutic strategies, peptide-based vaccines have attracted attention for their safety, specificity, and capacity to elicit tumor-directed T cell responses. Over the past two decades, several platforms targeting tumor-associated or tumor-specific antigens, including EGFRvIII, WT1, and survivin, have advanced into clinical trials. While early-phase studies demonstrated immunogenicity and occasional survival benefits, phase III trials have largely failed to confirm durable efficacy, underscoring the challenges posed by the ongoing complexity of tumor evasion mechanisms among which down regulation of MHC (HLA) expression in tumor cells, lack or reduced tumor antigen expression and a suppressive tumor microenvironment certainly play a role.</div></div><div><h3>Main body</h3><div>As far as tumor antigens, recent insights also question the centrality of neoantigens, highlighting instead the immunogenicity of shared tumor-associated antigens, which may provide a more reliable foundation for broadly applicable vaccines in GBM. A major barrier to efficacy remains impaired antigen presentation, particularly the downregulation of MHC-II pathways. In this context, strategies leveraging the transcriptional activator CIITA to restore MHC-II expression hold promise both for reprogramming GBM cells into effective antigen-presenting cells and for the isolation of new families of MHC class II-bound peptides relevant for the triggering of tumor-specific CD4⁺ T cells.</div></div><div><h3>Conclusion</h3><div>This new approach could pave the way for next-generation peptide vaccines, particularly when integrated with combinatorial modalities such as checkpoint inhibitors, myeloid-targeted therapies, or oncolytic viruses.</div></div>","PeriodicalId":8934,"journal":{"name":"Biomedical Journal","volume":"49 4","pages":"Article 100974"},"PeriodicalIF":6.3,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13453455/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147580091","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}