BMC Immunology最新文献

{"title":"In vitro differentiation of common lymphoid progenitor cells into B cell using stromal cell free culture system.","authors":"Pan Yang, Xiaoling Chen, Hao Wen, Meiling Yu, Haili Yu, Li Wang, Liang Gong, Lintao Zhao","doi":"10.1186/s12865-025-00694-8","DOIUrl":"10.1186/s12865-025-00694-8","url":null,"abstract":"<p><p>The OP9 culture system is an important in vitro model for B cell development. However, the complex nature of operations and the intrinsic variability of stromal cell functionality, which can be influenced by factors such as radiation exposure or contamination, pose considerable challenges to their wider application. Currently, there exists a paucity of studies documenting in vitro B cell differentiation culture systems that exclude stromal cells, and the experimental methodologies available for reference remain limited. This report elucidates a robust stromal cell-free culture system. Specifically, bovine serum albumin (BSA) or fetal bovine serum (FBS), in conjunction with interleukin-7 (IL-7), Flt3 ligand (Flt3L), and stem cell factor (SCF), were incorporated into X-VIVO15 medium. This system proficiently facilitates the directed differentiation of common lymphoid progenitor cells (CLP), defined as lineage-CD127 + CD117^lowsca-1^lowCD135+, into B lymphocytes in vitro, achieving an amplification factor of up to one hundredfold.We examined the roles of IL-7, Flt3L and SCF in differentiation of B cells from CLP in this culture system. Our findings indicate that IL-7 is a pivotal cytokine essential for B cell differentiation in vitro, demonstrating a notable synergistic impact when combined with SCF and FLT3L. Moreover, this system is capable of supporting the differentiation of hematopoietic stem cells (HSCs) and lymphoid-primed multipotent progenitor cells (LMPPs) into B cells in vitro. The findings substantiated the efficacy of the culture system in investigating the in vitro differentiation of bone marrow-derived progenitor cells into B cells and elucidated the specific roles of BSA, FBS and three cytokines (IL-7, FLT3L and SCF) in promoting efficient B lineage differentiation.</p>","PeriodicalId":9040,"journal":{"name":"BMC Immunology","volume":"26 1","pages":"12"},"PeriodicalIF":2.9,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11877881/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143555748","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":"Association of the systemic immune-inflammation index with clinical outcomes in acute myocardial infarction patients with hypertension.","authors":"Tingting Zheng, Chaodi Luo, Suining Xu, Xiyang Li, Gang Tian","doi":"10.1186/s12865-025-00690-y","DOIUrl":"10.1186/s12865-025-00690-y","url":null,"abstract":"<p><strong>Background: </strong>A new indicator of immunological and inflammatory condition, the Systemic Immunoinflammatory Index (SII), has been linked to a bad prognosis in a number of disorders.</p><p><strong>Methods: </strong>Two thousand three hundred seventeen ICU patients were admitted with hypertension and acute myocardial infarction (AMI). Patients were grouped according to their baseline SII tertile number into Q1, Q2, and Q3 groups. The main outcomes were death from all causes at 30 days, 365 days, cardiogenic shock, and congestive heart failure.</p><p><strong>Results: </strong>The case fatality rate increases with increasing SII. The correlation between SII and 30-day all-cause mortality [hazard ratio (HR) 1.765, 95% confidence interval (CI) 1.330-2.343 (Q3 versus Q1 group)], 365-day all-cause mortality [HR 2.713, 95% CI 2.250-3.272 (Q3 versus Q1 group), HR 1.603, 95% CI 1.312-1.959 (Q3 vs. Q1 group)], congestive heart failure [odds ratio (OR) 1.255, 95% CI 1.006-1.565 (Q2 vs. Q1 group), OR 1.565, 95% CI 1.220-2.009 (Q3 vs. Q1 group)] and cardiogenic shock [OR 1.930. 95% CI 1.271-2.974 (Q2 vs. Q1 group)] were all validated. According to subgroup analysis, individuals who had chosen to have CABG surgery had a stronger correlation between SII and a worse outcome. According to Kaplan-Meier (K-M) survival curves, patients in the Q3 group with SII had the highest rates of morbidity and death. The RCS curves demonstrated an essentially linear connection between SII and 30 days, 365 days, and congestive heart failure even after controlling for covariates.</p><p><strong>Conclusions: </strong>SII was substantially correlated with 30-day all-cause mortality, 365-day all-cause mortality, in-hospital congestive heart failure, and cardiogenic shock in patients who had both hypertension and acute myocardial infarction. In individuals with acute myocardial infarction and hypertension, a greater SII would be regarded as an independent risk factor for a higher death rate.</p>","PeriodicalId":9040,"journal":{"name":"BMC Immunology","volume":"26 1","pages":"10"},"PeriodicalIF":2.9,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11869594/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143522655","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 BTK as an immune-related biomarker for Hashimoto's thyroiditis by integrated bioinformatic analysis.","authors":"Yingzhao Liu, Zhangwei Zhu, Qian Xu, Juan Xu, Jie Xing, Shengjun Wang, Huiyong Peng","doi":"10.1186/s12865-025-00691-x","DOIUrl":"10.1186/s12865-025-00691-x","url":null,"abstract":"<p><strong>Background: </strong>Hashimoto's thyroiditis (HT) is one of the most common autoimmune disorders characterized by diffuse enlargement of the thyroid gland, lymphocyte infiltration, and thyroid-specific autoantibodies. Cellular and humoral immune disorders have been implicated in the development of HT. However, little is known regarding the role of immune-related molecules in HT. This study was aimed to identify key immune-related biomarkers in HT by using bioinformatic analysis.</p><p><strong>Method: </strong>Integration of the sequencing data from HT and normal control (NC) in the GSA and GTEx databases yielded a dataset named NGS. The GSE138198 dataset from the GEO database was downloaded as a validation set. WGCNA analysis was performed to identify key modules associated with HT. Lasso regression analysis (LASSO) and random forest (RF) were performed to determine potential diagnostic biomarkers. The potential value was assessed by using receiver operating characteristic (ROC) curve analysis. CIBERSORT algorithm was used to evaluate the infiltration of immune cells in HT and NC samples. The transcript levels of verified genes from expanded samples were detected by quantitative real-time PCR.</p><p><strong>Results: </strong>A total of 1,401 differentially expressed genes (DEGs) were identified in HT patients. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses indicated that these DEGs were predominantly enriched in immune-related pathways. Furthermore, 192 immune-related genes were identified in HT through the intersection of WGCNA modules, DEGs, and the IRGs. Among them, two upregulated genes ((Bruton's tyrosine kinase, BTK) and CD19) showed the potential diagnostic value for HT by using machine learning. The ROC curve analysis revealed that BTK had a higher diagnostic value than CD19 across two datasets. Intriguingly, only BTK expression was upregulated in the peripheral blood mononuclear cells of HT patients, and was significantly positively correlated with the serum levels of thyroid autoantibodies. Further studies confirmed a significant positive correlation between BTK and increased proportions of plasma cells in HT patients.</p><p><strong>Conclusion: </strong>This study identified BTK was significantly increased in HT patients, which might be the involved in the pathogenesis of HT by regulating plasma cells and represented a potential immune-related biomarker of HT.</p>","PeriodicalId":9040,"journal":{"name":"BMC Immunology","volume":"26 1","pages":"11"},"PeriodicalIF":2.9,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11869739/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143531061","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":"Effect of conditioned medium from miRNA-34a transfected gastric cancer-associated fibroblast on peripheral blood mononuclear cells.","authors":"Mozhgan Esmaili, Narjes Jafari, Fatemeh Ahmadzadeh, Seyed Mohammad Valizadeh Toosi, Saeid Abediankenari","doi":"10.1186/s12865-025-00688-6","DOIUrl":"10.1186/s12865-025-00688-6","url":null,"abstract":"<p><strong>Background: </strong>Cancer-associated fibroblast (CAF) cells play an important role in gastric malignancy. MiRNA dysregulation has been detected in CAF cells, which is related to the tumor progression ability of these cells. Therefore, this study aimed to evaluate the function of miRNA34a in CAF cells in gastric carcinoma.</p><p><strong>Method: </strong>We transiently transfected miRNA-34a mimic in CAF cells and examined the effect of the overexpressed miRNA on PD-L1 expression using real-time PCR. Next, we evaluated the role of transfected CAF-conditioned medium (CM) on the immune response and viability of gastric cancer cell lines.</p><p><strong>Results: </strong>We have shown that miRNA-34a significantly reduced PD-L1 expression in CAF cells (p < 0.05). However, the conditioned medium of transfected cells had no significant effect on the immune response. We also found that CM of miRNA-34a transfected CAF cells significantly suppressed gastric cancer cell line viability relative to the control group (P < 0.05).</p><p><strong>Conclusion: </strong>We indicated that CM of miRNA-34a transfected CAF can reduce gastric cancer cell line proliferation. Additionally, miRNA-34a in these cells may improve immune response via PD-L1 reduction. Thus, miRNA-34a could be a potential therapeutic agent in gastric cancer treatment.</p><p><strong>Clinical trial number: </strong>Not applicable.</p>","PeriodicalId":9040,"journal":{"name":"BMC Immunology","volume":"26 1","pages":"9"},"PeriodicalIF":2.9,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11854116/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143498967","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":"Pharmacokinetic interaction assessment of an HIV broadly neutralizing monoclonal antibody VRC07-523LS: a cross-protocol analysis of three phase 1 trials in people without HIV.","authors":"Tariro D Chawana, Stephen R Walsh, Lynda Stranix-Chibanda, Zvavahera M Chirenje, Chenchen Yu, Lily Zhang, Kelly E Seaton, Jack Heptinstall, Lu Zhang, Carmen A Paez, Theresa Gamble, Shelly T Karuna, Philip Andrew, Brett Hanscom, Magdalena E Sobieszczyk, Srilatha Edupuganti, Cynthia L Gay, Sharon B Mannheimer, Christopher B Hurt, Kathryn E Stephenson, Laura L Polakowski, Hans Spiegel, Margaret Yacovone, Stephanie Regenold, Catherine Yen, Jane Ag Baumblatt, Lucio Gama, Dan H Barouch, Estelle Piwowar-Manning, Richard A Koup, Georgia D Tomaras, Ollivier Hyrien, Alison C Roxby, Yunda Huang","doi":"10.1186/s12865-025-00687-7","DOIUrl":"10.1186/s12865-025-00687-7","url":null,"abstract":"<p><p>VRC07-523LS is a safe and well-tolerated monoclonal antibody (mAb) targeting the CD4 binding site on the HIV envelope (Env) trimer. Efficacy of VRC07-523LS, in combination with mAbs targeting other HIV epitopes, will be evaluated in upcoming trials to prevent HIV acquisition in adults. However, differences in the pharmacokinetics (PK) of VRC07-523LS when administered alone vs. in combination with other mAbs have not been formally assessed. We performed a cross-protocol analysis of three clinical trials and included data from a total of 146 adults without HIV who received intravenous (n = 95) or subcutaneous (n = 51) VRC07-523LS, either alone ('single'; n = 100) or in combination with 1 or 2 other mAbs ('combined'; n = 46). We used an open, two-compartment population PK model to describe serum concentrations of VRC07-523LS over time, accounting for inter-individual variabilities. We compared individual-level PK parameters between the combined vs. single groups using the targeted maximum likelihood estimation method to adjust for participant characteristics. No significant differences were observed in clearance rate, inter-compartmental clearance, distribution half-life, or total VRC07-523LS exposure over time. However, for the combined group, mean central volume of distribution, peripheral volume of distribution, and elimination half-life were slightly greater, corresponding to slightly lower predicted concentrations early post-administration with high levels being maintained in both groups. These results suggest potential PK interactions between VRC07-523LS and other mAbs, but with small clinical impact in the context of HIV prevention. Our findings support coadministration of VRC07-523LS with other mAbs, and the use of the developed PK models to design future trials for HIV prevention.</p>","PeriodicalId":9040,"journal":{"name":"BMC Immunology","volume":"26 1","pages":"8"},"PeriodicalIF":2.9,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11837431/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143447943","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":"Detecting the preoperative peripheral blood systemic immune-inflammation index (SII) as a tool for early diagnosis and prognosis of gallbladder cancer.","authors":"Feng Liu, Pengyu Yin, Baoping Jiao, Zhiyong Shi, Feifei Qiao, Jun Xu","doi":"10.1186/s12865-025-00683-x","DOIUrl":"10.1186/s12865-025-00683-x","url":null,"abstract":"<p><strong>Objective: </strong>Evidence indicates that the systemic immune-inflammation index (SII) correlates with poor prognosis in various solid tumors. This retrospective study aimed to evaluate the diagnostic and prognostic significance of preoperative SII combined with tumor markers for early detection and prognosis of gallbladder cancer (GBC).</p><p><strong>Methods: </strong>Preoperative SII levels and serum tumor markers [carcinoembryonic antigen (CEA), carbohydrate antigen 125 (CA125), and carbohydrate antigen 19 - 9 (CA19-9)] were measured in GBC patients. Correlations and diagnostic efficacy were analyzed using Spearman correlation and receiver operating characteristic (ROC) curve analyses. The relationship between SII and clinical data was analyzed, and cumulative survival rates of the two groups were compared. Independent risk factors for poor prognosis in GBC patients were assessed using Kaplan-Meier curves and Cox multivariate analysis.</p><p><strong>Results: </strong>Preoperative SII, CEA, CA125, and CA19-9 levels were significantly elevated in GBC patients compared to those with benign lesions. SII positively correlated with CEA, CA125, and CA19-9 levels (r = 0.434, 0.570, 0.614, respectively, all P < 0.001). The area under the ROC curve (AUC) for the combination of SII, CEA, CA125, and CA19-9 was 0.877 for early GBC diagnosis and 0.923 for predicting postoperative mortality, outperforming each marker individually. An SII threshold > 889.52 was predictive of postoperative death. High SII was associated with tumor size, differentiation, tumor-node-metastasis stage, lymph node metastasis, perineural invasion, surgical type, neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, and serum tumor marker levels. Kaplan-Meier analysis revealed poorer survival in the high SII group. Preoperative SII was identified as an IRF for poor prognosis in GBC patients.</p><p><strong>Conclusion: </strong>Preoperative SII correlates strongly with CEA, CA125, and CA19-9 levels. The combined use of SII and tumor markers offers high diagnostic value for early GBC detection and robust predictive value for postoperative mortality. Preoperative SII serves as an IRF for poor prognosis in GBC patients.</p>","PeriodicalId":9040,"journal":{"name":"BMC Immunology","volume":"26 1","pages":"7"},"PeriodicalIF":2.9,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11834489/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143447940","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":"Combining machine learning with external validation to explore necroptosis and immune response in moyamoya disease.","authors":"Yutong Liu, Kexin Yuan, Linru Zou, Chengxu Lei, Ruichen Xu, Shihao He, Yuanli Zhao","doi":"10.1186/s12865-025-00686-8","DOIUrl":"10.1186/s12865-025-00686-8","url":null,"abstract":"<p><p>Moyamoya disease (MMD) is a rare chronic vascular disease leads to cognitive impairment and stroke with its etiology unknown. The relationship between necroptosis or necroinflammation and MMD pathogenesis was poorly understood. Differentially expressed necroinflammation and necroptosis related genes (DE-NiNRGs) were selected based on the public gene expression data from Gene Expression Omnibus (GEO) and validated by our self-test data of MMD patients and control group. Functional enrichment analysis, PPI network and multi-factors regulation network construction of DE-NiNRGs were employed to discover the connections between these genes. DE-NiNRGs and immune cells correlation analysis provided evidence for the relationship between DE-NiNRGs and necroinflammation in MMD patients. We then established an MMD prediction model using support vector machine (SVM) and selected DE-NiNRGs as features. The DE-NiNRGs based MMD prediction model had excellent performance on test set with the area under the curve (AUC) higher than 0.9. Four genes, PTGER3, ANXA1, ID1, and IL1R1, that contributed significantly to the SVM model and passed the test of validation set are key genes in DE-NiNRGs. The upregulation of PTGER3 expression indicated that necroptosis and angiogenesis were promoted in MMD patients, whereas the downregulation of ANXA1 expression indicated that the migration and differentiation of immune cells are closely related to MMD pathogenesis. These findings provided new inspiration for our study of the immune-related pathogenesis and therapeutic targets of MMD.</p>","PeriodicalId":9040,"journal":{"name":"BMC Immunology","volume":"26 1","pages":"6"},"PeriodicalIF":2.9,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11823220/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143413031","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":"Single-cell characterization of the immune heterogeneity of pulmonary hypertension identifies novel targets for immunotherapy.","authors":"Pan Jiang, Huai Huang, Mengshi Xie, Zilong Liu, Lijing Jiang, Hongyu Shi, Xiaodan Wu, Shengyu Hao, Shanqun Li","doi":"10.1186/s12865-025-00684-w","DOIUrl":"10.1186/s12865-025-00684-w","url":null,"abstract":"<p><strong>Background: </strong>Pulmonary arterial hypertension (PAH) is a critical cardiopulmonary vascular disorder marked by the progressive elevation of pulmonary artery pressure, increased pulmonary vascular resistance, and eventual right heart failure. Research has shown that various immune cells play a significant role in the pathogenesis of PAH, both in patients diagnosed with the condition and in experimental models of PAH. Cell-cell communication is important for PAH progression and therapies, while the global cell landscape of intercellular signaling has not been elucidated.</p><p><strong>Methods: </strong>We performed single-cell RNA sequencing on NCBI Gene Expression Omnibus (GEO) databases GSE169471, GSE 210248, GSE228643 and GSE244781, and analyzed lung tissue samples across healthy controls and PAH patients. In total, approximately 124,561 cells were analyzed and a total 34 clusters were identified. We integrated the sequencing results of multiple samples and used an enhanced single-cell sequencing workflow to overcome the limitations of a single study.</p><p><strong>Results: </strong>In this study, we elucidated the functional characteristics and potential regulatory interactions of several cell subpopulations that have not been previously documented in similar research. We constructed a comprehensive landscape of cell communications at the single-cell resolution, which is expected to significantly advance the development of personalized diagnostic and therapeutic strategies for PAH. We demonstrated the transcriptomic features of different cell types in PAH patients. We presented an in-depth analysis of T cell subsets, myeloid cell heterogeneity and a comprehensive analysis of SMCs and FBs subsets in PAH. T cell heterogeneity and functional dynamics were exhibited in PAH, which suggests that targeting cytotoxic regulation may be a potential therapeutic strategy. Significant changes and potential functions of myeloid cell subsets in PAH patients and we especially focused on GPNMB⁺ macrophages. In addition, CellChat and NicheNet analyses reveal altered intercellular communication and dys-regulated signaling pathways in PAH progression. The enhanced MIF and IL-1 signaling suggests that the induced inflammatory response in PAH is greatly driven.</p><p><strong>Conclusions: </strong>We systematically explored the immune heterogeneity and population and target cells in PAH, which may be valuable for developing new and precise therapies.</p>","PeriodicalId":9040,"journal":{"name":"BMC Immunology","volume":"26 1","pages":"5"},"PeriodicalIF":2.9,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11809027/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143389993","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":"Increased PD-1 expression in livers associated with PD-1-antibody-induced hepatotoxicity.","authors":"Miro Saarela, Essi Parviainen, Ana Lleo, Luca di Tommaso, Hanna Raunio, Krista Kankaanranta, Katri Vuopala, Aino Rönkä, Sini Nurmenniemi, Raija Kallio, Arja Jukkola, Katri S Selander","doi":"10.1186/s12865-025-00682-y","DOIUrl":"10.1186/s12865-025-00682-y","url":null,"abstract":"<p><p>Vanishing bile duct syndrome (VBDS) is a serious drug induced liver injury characterized by chronic cholestasis and loss of intrahepatic bile ducts. VBDS has been reported also following checkpoint inhibitor treatment. We compared CD3 + , CD4 + , CD8 + , CD20 + , CD57 + , PD-1 + and PD-L1 + lymphocyte infiltrates in liver biopsies of patients that encountered VBDS (n = 2) or hepatotoxicity (n = 3) after pembrolizumab (n = 4) or nivolumab (n = 1) treatment with samples from normal liver (n = 10), non-alcohol steatohepatitis (NASH, n = 10), primary biliary cholangitis (PBC, n = 10) or pembrolizumab-treated patients without adverse events (n = 2). Notably, none of the cancer patients had primary nor metastatic liver tumors. We also studied direct growth effects of pembrolizumab on primary human intrahepatic biliary epithelial cells (HIBEpiC) in vitro. Liver sections of all checkpoint inhibitor- treated patients exhibited significantly higher CD3 + infiltration than normal livers, and significantly higher PD-L1 + , CD4 + and CD8 + infiltration, than other groups. PD-1 + infiltration was significantly increased in livers of patients with severe hepatic adverse event. CD57 + infiltration was similar in normal livers, NASH- and PBC groups, but highly increased in the checkpoint inhibitor-treated patients. Immune cell infiltrates were similar between NASH and normal livers. PBC samples had significantly higher CD3 + , CD4 + , CD8 + and CD20 + infiltrates than normal livers. HIBEpiC express PD-L1 but pembrolizumab did not affect their viability in vitro. Our findings suggest that VBDS is not due to direct cytotoxicity of checkpoint inhibitors and that the immunological attack against livers induced by these drugs is different from other cholestatic liver conditions.Biological insight: Checkpoint inhibitors upregulate PD-1 and PD-L1, as well as cytotoxic CD57 + cells in the non-cancerous liver tissues and this may be associated with checkpoint inhibitor-induced hepatotoxicity.</p>","PeriodicalId":9040,"journal":{"name":"BMC Immunology","volume":"26 1","pages":"4"},"PeriodicalIF":2.9,"publicationDate":"2025-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11755961/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143022071","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":"IL-6 and PD-1 antibody blockade combination therapy regulate inflammation and T lymphocyte apoptosis in murine model of sepsis.","authors":"Song I Lee, Na Young Kim, Chaeuk Chung, Dongil Park, Da Hyun Kang, Duk Ki Kim, Min-Kyung Yeo, Pureum Sun, Jeong Eun Lee","doi":"10.1186/s12865-024-00679-z","DOIUrl":"10.1186/s12865-024-00679-z","url":null,"abstract":"<p><strong>Background: </strong>Interleukin-6 (IL-6) plays a central role in sepsis-induced cytokine storm involving immune hyperactivation and early neutrophil activation. Programmed death protein-1 (PD-1) is associated with sepsis-induced immunosuppression and lymphocyte apoptosis. However, the effects of simultaneous blockade of IL-6 and PD-1 in a murine sepsis model are not well understood.</p><p><strong>Results: </strong>In this study, sepsis was induced in male C57BL/6 mice through cecal ligation and puncture (CLP). IL-6 blockade, PD-1 blockade, or combination of both was administered 24 h after CLP. Peripheral blood count, cytokine level, lymphocyte apoptosis in the spleen, neutrophil infiltration in the lungs and liver, and survival rate were measured. The mortality rate of the IL-6/PD-1 group was lower, though not statistically significant (p = 0.164), than that of CLP mice (75.0% vs. 91.7%). The IL-6/PD-1 group had lower neutrophil percentage and platelet count compared with the CLP group; no significant difference was observed in other cytokine levels. The IL-6/PD-1 group also showed reduced T lymphocyte apoptosis in the spleen and decreased neutrophil infiltration in the liver and lungs.</p><p><strong>Conclusions: </strong>IL-6/PD-1 dual blockade reduces neutrophil infiltration, lymphocyte apoptosis, and bacterial burden while preserving tissue integrity in sepsis. Although the improvement in survival was not statistically significant, these findings highlight its potential as a therapeutic approach in sepsis.</p>","PeriodicalId":9040,"journal":{"name":"BMC Immunology","volume":"26 1","pages":"3"},"PeriodicalIF":2.9,"publicationDate":"2025-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11731149/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142977507","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}