Clinical and Experimental Medicine最新文献

{"title":"TPM4 influences the initiation and progression of gastric cancer by modulating ferroptosis via SCD1.","authors":"Ling-Lin Zhao, Yu-Jun Liu, Qi-Jing Guo, Nan Yan, Jie Yang, Jing-Qi Han, Xiao-Hong Xie, Yu-Shuang Luo","doi":"10.1007/s10238-025-01629-8","DOIUrl":"https://doi.org/10.1007/s10238-025-01629-8","url":null,"abstract":"<p><p>Gastric cancer (GC) is a deadly disease with poor prognosis and few treatment options. Tropomyosin 4 (TPM4) is an actin-binding protein that stabilizes the cytoskeleton of cells and has an unclear role in GC. This study aimed to elucidate the role and underlying mechanisms of TPM4 in GC pathogenesis. The expression and diagnostic and prognostic value of TPM4 in GC were analyzed using bioinformatics. A nomogram based on TPM4 expression was created and validated with an external cohort. TPM4-knockdown GC cells and xenograft models in nude mice were used to study the function of TPM4 in vitro and in vivo. Proteomic and rescue experiments confirmed the regulatory effect of TPM4 on stearoyl-CoA desaturase 1 (SCD1) in GC. Immunohistochemistry verified the expression and correlation of the TPM4 and SCD1 proteins in GC tissues. Our study identified TPM4 as an oncogene in GC, suggesting its potential diagnostic and prognostic value. The TPM4-based nomogram showed potential prognostic value for clinical use. TPM4 knockdown inhibited GC cell proliferation, induced ferroptosis, and slowed tumor growth in vivo, which is achieved by inhibiting SCD1 expression. Immunohistochemical analysis of GC tissues revealed elevated expression levels of both TPM4 and SCD1 proteins, with a positive correlation observed between their expression. TPM4 is a promising target for new diagnostic, prognostic, and therapeutic strategies for GC. Downregulation of TPM4 inhibits GC cell growth and induces ferroptosis by suppressing SCD1 expression.</p>","PeriodicalId":10337,"journal":{"name":"Clinical and Experimental Medicine","volume":"25 1","pages":"115"},"PeriodicalIF":3.2,"publicationDate":"2025-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11991984/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143985744","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Circulating miR-485-5p as a potential diagnostic and prognostic biomarker for HCV-related hepatocellular carcinoma.","authors":"Gamalat A Elgedawy, Naglaa S Elabd, Asmaa M Elbrolosy, Suzan M El-Morshedy, Ayman El-Gamal, Mai Abozeid, Mervat Abdelkreem, Sama S Eleowa, Marwa L Helal","doi":"10.1007/s10238-025-01625-y","DOIUrl":"https://doi.org/10.1007/s10238-025-01625-y","url":null,"abstract":"<p><p>Hepatitis C virus (HCV) is the predominant viral cause of hepatocellular carcinoma (HCC). Early detection and use of reliable biological markers can improve survival for HCC patients. MiR-485-5p was identified as a tumor-suppressing microribonucleic acid (miRNA) in some human cancers and was recently found to be downregulated in HCC tissues, signifying its utility as a promising biomarker. We aimed to investigate the potential role of circulating miR-485-5p as a novel diagnostic and prognostic biomarker for HCV-related HCC. This case-control study included 50 patients with HCC associated with HCV, 50 patients with HCV-related liver cirrhosis, and 50 healthy controls. History gathering, physical examination, laboratory, and imaging assessments were performed. A quantitative real-time polymerase chain reaction was used to measure miR-485-5p levels. Serum miR-485-5p values demonstrated a stepwise decline pattern from the control group to cirrhotic patients, with the HCC group exhibiting the lowest levels (p < 0.001). HCC patients with early BCLC stages had significantly lower miR-485-5p levels than those with late stages (p = 0.004). The miR-485-5p displayed a better performance in predicting HCV-related HCC with a greater area under the ROC curve (AUC) than alpha-fetoprotein (AFP) (AUC and sensitivity 0.921 and 92.0 versus 0.704 and 64.0, respectively) (p < 0.001). Also, its performance in predicting HCC prognosis surpassed that of AFP (AUC and sensitivity 0.872 and 85.19 versus 0.695 and 62.96, respectively) (p < 0.001). Circulating miR-485-5p is a promising, accurate, and noninvasive biomarker for the early detection and prediction of prognosis in patients with HCV-linked HCC.</p>","PeriodicalId":10337,"journal":{"name":"Clinical and Experimental Medicine","volume":"25 1","pages":"110"},"PeriodicalIF":3.2,"publicationDate":"2025-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11985578/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143955115","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Isolation and characterization of extracellular vesicles from EGFR mutated lung cancer cells.","authors":"Dian Jamel Salih, Katrin S Reiners, Roberta Alfieri, Ahmed Mohammed Salih, Zulema Antonia Percario, Mariantonietta Di Stefano, Sollitto Francesco, Elisabetta Affabris, Gunther Hartmann, Teresa Santantonio","doi":"10.1007/s10238-025-01643-w","DOIUrl":"https://doi.org/10.1007/s10238-025-01643-w","url":null,"abstract":"<p><p>The epidermal growth factor receptor (EGFR) signaling pathway is essential for cellular processes such as proliferation, survival, and migration. Dysregulation of EGFR signaling is frequently observed in non-small cell lung cancer (NSCLC) and is associated with poor prognosis. This study aims to isolate and characterize extracellular vesicles (EVs) released by mutant EGFR lung cancer cell line PC9 and compare them with wild-type EGFR lung cancer cell line A549, while also evaluating the effect of gefitinib treatment on EV secretion and cargo composition. The two lung cancer cell lines were cultured with 2% EV-free serum, and EVs were subsequently isolated by differential ultra centrifugation. EVs were characterized by nanoparticle tracking analysis (NTA) and transmission electron microscopy (TEM) for quantification size and shape determination. Western blot analysis confirmed the enrichment and purity of isolated EVs. Results showed that EGFR mutation significantly increased EV release and altered their size, compared to EVs released by wild-type EGFR cells. In addition to classical EV markers such as CD81, Flotillin- 1, and TSG101, Western blot analysis also detected phosphorylated EGFR (p-EGFR) selectively packaged into EVs from PC9 cells. Gefitinib treatment significantly reduced EV secretion in PC9 cells and led to a marked decrease in p-EGFR incorporation into EVs, indicating that EV biogenesis and compostion are modulated by active EGFR signaling. In conclusion, this study highlights the significant influence of EGFR activation on EV secretion and cargo composition while demonstrating that EGFR inhibition via gefitinib alters EV-mediated signaling in lung cancer cells. These findings provide insights into tumor behavior, EV-mediated oncogenic communication, and the potential use of EVs as biomarkers and therapeutic targets in NSCLC.</p>","PeriodicalId":10337,"journal":{"name":"Clinical and Experimental Medicine","volume":"25 1","pages":"114"},"PeriodicalIF":3.2,"publicationDate":"2025-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11985682/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143975390","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluation of cytomorphological examination in the diagnosis of pleural effusion.","authors":"Xiaoting Chen, Yongyu Li, Hongyan Wang, Kaizhen Wen","doi":"10.1007/s10238-025-01642-x","DOIUrl":"https://doi.org/10.1007/s10238-025-01642-x","url":null,"abstract":"<p><p>Cytological examination serves as a crucial diagnostic tool for pleural effusion, with its diagnostic efficacy influenced by variations in specimen processing and staining techniques. Cellular morphological analysis of pleural effusions was performed using Wright-Giemsa staining to assess its diagnostic accuracy and clinical utility in differentiating the various etiologies of exudative pleural effusion. A routine examination was conducted on 2305 cases of unexplained pleural effusion, followed by cellular classification and morphological analysis in 1376 cases identified as exudative effusion. Among the 479 patients with malignant tumors, cytomorphological examination identified malignant cells in 295 patients, resulting in a clinical diagnosis coincidence rate of 98.6%. Abnormal cells, including malignant and heterogeneous nuclear cells, were observed in 364 cases, yielding a detection rate of 76.0%. The proportion of positive malignant cells in the newly diagnosed patient group was significantly higher than that in the previously diagnosed group (P < 0.01). Cytological analysis revealed the presence of bacteria, fungi, and phagocytes in 51 out of 1376 cases. The positivity rate for multiple bacterial infections detected through cytology was significantly greater than that identified by culture (P < 0.01). Additionally, various special morphologies and pathogens, which are rare in clinical practice, were detected, including mixed metastasis of small cell lung carcinoma and adenocarcinoma cells, as well as concurrent infections with Talaromyces marneffei and Pneumocystis jirovecii. This method enables the rapid and comprehensive differentiation between malignant tumors, tuberculosis, pneumonia, and rare exudative pleural effusions resulting from specific clinical conditions.</p>","PeriodicalId":10337,"journal":{"name":"Clinical and Experimental Medicine","volume":"25 1","pages":"112"},"PeriodicalIF":3.2,"publicationDate":"2025-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11985587/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143968771","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification of glucuronic acid as a biomarker of poor prognosis in acute myeloid leukemia based on plasma metabolomics.","authors":"Jinrong Yang, Zixu Wang, Kun Wu, Jingyan Ruan, Bo Nie, Qiang Zhou, Liyin Li, Li Luo, Fujia Zhang, Mingxia Shi, Yun Zeng","doi":"10.1007/s10238-025-01605-2","DOIUrl":"https://doi.org/10.1007/s10238-025-01605-2","url":null,"abstract":"<p><p>Metabolic abnormalities have been identified in various solid tumors and hematologic diseases, with reprogramming of central carbon metabolism occurring to promote disease progression. However, the metabolic profile of central carbon in acute myeloid leukemia (AML) remains unknown. We employed targeted metabolomics to analyze the alterations in central carbon metabolites present in the blood of acute myeloid leukemia (AML) patients. Models constructed using orthogonal partial least squares discriminant analysis (OPLS-DA) were utilized to evaluate intergroup differences in metabolite levels. Furthermore, a public database facilitated the kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analysis. Additionally, metabolites exhibiting significant differences were selected, and their effects on the proliferation and drug resistance of human myeloid leukemia cell lines were validated in vitro using CCK-8 analysis, MTT assays, and flow cytometry. Our results indicated that 27 targeted metabolites were up-regulated and eight targeted metabolites were down-regulated in the AML group. These metabolites were primarily enriched in pathways related to the biosynthesis of cofactors, glyoxylate and dicarboxylate metabolism, glucagon signaling, 2-oxocarboxylic acid metabolism, biosynthesis of amino acids, the citrate cycle (TCA cycle), and central carbon metabolism in cancer. Notably, significant changes were observed in malic acid, alpha-ketoisovaleric acid, and glucuronic acid. In vitro experiments demonstrated that exogenous glucuronic acid can promote the growth and drug resistance of human AML cells. In conclusion, this study reveals alterations in central carbon metabolites in the blood of AML patients and identifies metabolites that may play a role in AML development and drug resistance.</p>","PeriodicalId":10337,"journal":{"name":"Clinical and Experimental Medicine","volume":"25 1","pages":"111"},"PeriodicalIF":3.2,"publicationDate":"2025-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11985698/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143956857","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hepatitis B virus infection after immunization: How serious it is? An updated review.","authors":"Arezoo Marjani, Seyed Moayed Alavian, Mohssen Nassiri Toosi, Seyed Hoda Alavian, Mohammad Foad Abazari, Azam Khamseh, Seyed Mohammad Jazayeri","doi":"10.1007/s10238-025-01645-8","DOIUrl":"https://doi.org/10.1007/s10238-025-01645-8","url":null,"abstract":"<p><p>Infection with hepatitis B virus (HBV) is one of the significant challenges worldwide. Despite the availability of antiviral drugs against this virus, the most critical strategy to prevent HBV infection is HB vaccination. Basically, despite widespread conventional HB vaccination, due to various reasons, including waning of hepatitis B surface antibody (HBsAb) titer after vaccination, the emergence of vaccine-escape mutants, failure to respond to the vaccine due to viral and host factors, levels of response in high-risk individuals and non-responders to conventional HB vaccination remains a major, unsolved and severe concern. This review focuses on the underlying reasons for conventional hepatitis B vaccination failures. It also suggests solutions to overcome these failures by highlighting significant advances in vaccination, including hepatitis B third-generation vaccines and adjuvanted hepatitis B vaccines as efficient alternatives to second-generation vaccines. Potentially, these new strategies will compensate for the shortcomings caused by second-generation vaccines. Adherence to these denouements has a significant role in preventing the circulation of HBV among individuals and reducing the global burden of HBV-related diseases.</p>","PeriodicalId":10337,"journal":{"name":"Clinical and Experimental Medicine","volume":"25 1","pages":"113"},"PeriodicalIF":3.2,"publicationDate":"2025-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11985588/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143980694","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A study of booster dose influenza vaccination responses compared to standard dose in lupus patients: an open-labeled, randomized controlled study.","authors":"Sasicha Yingyounyong, Pintip Ngamjanyaporn, Prapaporn Pisitkun, Kobporn Boonnak, Thanitta Suangtamai, Supranee Thongpradit, Porpon Rotjanapan","doi":"10.1007/s10238-025-01639-6","DOIUrl":"https://doi.org/10.1007/s10238-025-01639-6","url":null,"abstract":"<p><p>Despite receiving an annual influenza vaccination, lupus patients showed a decline in immunological responses for various reasons. This study aimed to assess immune responses after booster- (BD) and standard-dose (SD) quadrivalent influenza vaccine and the adverse events and incidence of influenza infection among lupus patients. A randomized controlled trial was conducted between March 2021 and May 2022 at Ramathibodi Hospital. All lupus patients were stratified into two groups depending on the depth of immunosuppressive therapy and randomized to receive either BD or SD. Hemagglutination inhibition assay (HAI) before vaccination and 4 weeks after completion of the vaccination series were assessed. The incidence of influenza infection and vaccine-associated adverse events were recorded. A total of 109 lupus patients completed the HAI analysis. 54/109 patients were in high- (HI), and 55/109 were in low-level immunosuppressive (LI) groups. Focusing at the rates to achieve HAI ≥ 1:160, in the LI group, the rates after SD were 85.5% for H1N1, 69.2% for H3N2/Hongkong, 82.8% for H3N2/Cambodia, 85.5% for B/Victoria, and 81.8% for B/Yamagata. After BD, the HAI titer rates of ≥ 1:160 cut point were increased in all strains, approaching 100%, similar to the HI group. There was one documented influenza infection during the 12-month follow-up period in LI who received SD. No serious adverse events associated with influenza vaccination were recorded. A booster dose of influenza vaccination may provide a higher HAI titer among lupus patients. The booster influenza vaccine regimen was considered safe in the BD group. Thai Clinical Trials Registry: TCTR20230610003.</p>","PeriodicalId":10337,"journal":{"name":"Clinical and Experimental Medicine","volume":"25 1","pages":"109"},"PeriodicalIF":3.2,"publicationDate":"2025-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11982163/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143980396","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Angiogenesis-related gene signature for prognostic prediction and immune microenvironment characterization in diffuse large B-cell lymphoma.","authors":"Chuanming Lin, Shuiling Xie, Menger Wang, Bin Yang, Jianzhen Shen","doi":"10.1007/s10238-025-01628-9","DOIUrl":"10.1007/s10238-025-01628-9","url":null,"abstract":"<p><p>Diseases often result from multiple factors, and angiogenesis-related genes (ARGs) have been demonstrated to be associated with cancer. However, their role in diffuse large B-cell lymphoma (DLBCL) has not been fully elucidated. ARGs associated with DLBCL prognosis were identified utilizing Cox regression and LASSO analyses. A prognostic model was constructed based on 7 ARGs, and its biological function was analyzed. Differences in the tumor immune microenvironment based on the prognostic signature were evaluated. Finally, DLBCL cell experiments confirmed the differential expression of genes in DLBCL. The prognostic value of ARGs in DLBCL patients was comprehensively analyzed for the first time, identifying 7 ARGs with prognostic significance. A prognostic risk model was constructed based on these 7 ARGs and validated on an independent external DLBCL dataset. In DLBCL patients, this prognostic feature was an independent risk factor and significantly correlated with clinical characteristics. This feature was also associated with the immune microenvironment of DLBCL. DLBCL cell experiments confirmed significant expression of the 7 ARGs in DLBCL cells. This research provides a fundamental theoretical basis for improving the diagnosis and treatment of DLBCL in clinical practice.</p>","PeriodicalId":10337,"journal":{"name":"Clinical and Experimental Medicine","volume":"25 1","pages":"108"},"PeriodicalIF":3.2,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11978719/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143810637","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Biosimilars versus biological therapy in inflammatory bowel disease: challenges and targeting strategies using drug delivery systems.","authors":"Ahmed Aljabri, Ghareb M Soliman, Yasmin N Ramadan, Mohammed A Medhat, Helal F Hetta","doi":"10.1007/s10238-025-01558-6","DOIUrl":"10.1007/s10238-025-01558-6","url":null,"abstract":"<p><p>Inflammatory bowel disease (IBD) is a multifactorial illness with a climbing prevalence worldwide. While biologics are commonly prescribed especially for severe cases, they may worsen patients' outcomes due to financial burden. Consequently, there has been an increased focus on biosimilars to improve overall disease outcomes by maintaining similar efficacy and safety while minimizing the cost of therapy. Infliximab-dyyb was the first biosimilar approved by US-FDA for IBD. Since that, the US-FDA approved 14 biosimilars with different mechanisms of action and different routes of administration for IBD patients (four infliximab biosimilars, nine adalimumab biosimilars, and most recently one ustekinumab biosimilar). It should be noted that more biologics are in the pipeline as golimumab and natalizumab patents are set to expire in the near future, and biosimilars are now in pre-clinical to phase 3 trials. Different studies have evaluated biologics' effectiveness and safety and concluded that the majority of available biosimilars are efficacious and have similar adverse effect profiles compared to their reference biologics. It is worth mentioningthat post-marketing surveillance reports revealed some risks associated with biosimilars which should be taken into consideration in future research and clinical trials to avoid health hazards. Most biologics and biosimilars are administered parenterally which results in several drawbacks such as raised risk of infections, hypersensitivity, autoimmunity, development of malignancies, liver toxicity as well as worsening of heart failure. Several drug delivery systems based on passive and active targeting mechanisms are under active investigation to overcome these limitations. This review sheds light on the emergence of biologics and biosimilars as alternatives in IBD management, the differences between them, challenges and risks, and future perspectives in IBD therapy and new trends in drug delivery systems.</p>","PeriodicalId":10337,"journal":{"name":"Clinical and Experimental Medicine","volume":"25 1","pages":"107"},"PeriodicalIF":3.2,"publicationDate":"2025-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11972199/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143787775","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"PD-L1 importance in malignancies comprehensive insights into the role of PD-L1 in malignancies: from molecular mechanisms to therapeutic opportunities.","authors":"Mojdeh Soltani, Mohammad Abbaszadeh, Hamed Fouladseresht, Mark J M Sullman, Nahid Eskandari","doi":"10.1007/s10238-025-01641-y","DOIUrl":"10.1007/s10238-025-01641-y","url":null,"abstract":"<p><p>The phenomenon of upregulated programmed death-ligand 1 (PD-L1) expression is common in numerous human malignancies. The overexpression of PD-L1 significantly contributes to immune evasion because its interaction with the PD-1 receptor on activated T lymphocytes impairs anti-tumour immunity by neutralizing T cell stimulatory signals. Furthermore, beyond its immunological interface, PD-L1 possesses intrinsic capabilities that directly modulate oncogenic processes, fostering cancer cell proliferation and survival. This dual function of PD-L1 challenges the efficacy of immune checkpoint inhibitors and highlights its possible application as a direct target for therapy. Recent discoveries concerning the cancer cell-intrinsic signalling pathways of PD-L1 have significantly enhanced our understanding of the pathological implications linked to its tumour-specific expression. These entail the orchestration of tumour proliferation and viability, maintenance of cancer stem cell-like phenotypes, modulation of immune responses, as well as impacts on DNA repair mechanisms and transcriptional regulation. This review aims to deliver an exhaustive synthesis of PD-L1's molecular underpinnings alongside its clinical implications in a spectrum of cancers, spanning both solid neoplasms and haematological disorders. It underscores the necessity for an integrated understanding of PD-L1 in further refining therapeutic strategies and improving patient outcomes.</p>","PeriodicalId":10337,"journal":{"name":"Clinical and Experimental Medicine","volume":"25 1","pages":"106"},"PeriodicalIF":3.2,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11968484/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143779223","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}