American journal of clinical and experimental immunology最新文献

{"title":"Epigenetic regulatory mechanisms and translational applications in idiopathic pulmonary fibrosis.","authors":"Meng Jiang, Qilong Wang, Yinuo Lyu, Xinyang Hou, Xiumin Zhou","doi":"10.62347/WNML8981","DOIUrl":"10.62347/WNML8981","url":null,"abstract":"<p><p>Idiopathic pulmonary fibrosis (IPF) is a chronic, relentlessly progressive interstitial lung disease with limited treatment options and poor survival. Existing antifibrotic agents slow functional decline but do not halt or reverse established fibrosis, highlighting the need for IPF specific mechanistic understanding and new therapeutic targets. This review summarizes epigenetic regulatory mechanisms that are implicated in IPF, including DNA methylation, histone modifications, non-coding RNAs, and RNA modifications. These mechanisms can be viewed as interacting networks that reprogramme gene expression in alveolar epithelial cells, macrophages and fibroblasts, leading to impaired epithelial repair, profibrotic immune activation and maintenance of a chronically activated myofibroblast state. The contribution of cell type specific epigenetic signatures to chronic inflammation, disordered tissue remodelling and progressive extracellular matrix accumulation in IPF is underscored. Recent work that translates epigenetic insights into applications for IPF is also reviewed, with a focus on epigenetic marks and regulators as biomarkers for diagnosis, prognosis and treatment response, and as targets for small molecule drugs, nucleic acid based therapies and epigenome editing strategies. Overall the evidence assembled here provides a framework that focuses on IPF epigenetic regulation and can inform experimental design and support the development of more precise therapeutic approaches for patients with IPF.</p>","PeriodicalId":72163,"journal":{"name":"American journal of clinical and experimental immunology","volume":"15 1","pages":"14-27"},"PeriodicalIF":1.3,"publicationDate":"2026-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13000734/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147500850","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Management strategies for giant renal artery aneurysms: a systematic review and case report.","authors":"Lu Sun, Ziyi Fan, Jingyu Liu, Shijie Jiang, Yifan Zhu, Shiqing Li, Zhixin Ling, Feng Zhou","doi":"10.62347/YCOE8518","DOIUrl":"10.62347/YCOE8518","url":null,"abstract":"<p><strong>Background: </strong>Renal artery aneurysm (RAA) is a rare but potentially life-threatening condition. The definition of giant RAA is ≥ 50 mm. Although often asymptomatic, the risk of rupture increases significantly with size, posing a substantial threat. Giant RAAs have historically tended to be repaired using open surgery. At present, intravascular technology has become an alternative solution due to its advantage of less invasiveness.</p><p><strong>Objective: </strong>This study seeks to present a rare case of successful endovascular embolization for a giant renal aneurysm (RAA), while also systematically reviewing recent literature to compare the outcomes of surgical and endovascular treatments for giant RAA, and to describe management strategies for giant renal hemangiomas.</p><p><strong>Methods: </strong>We describe a case of a young man treated by endovascular coil embolization and had a large RAA. After the PRISMA guidelines were followed, a systematic literature review was carried out, initially identifying 347 studies. After screening and full-text review, 35 studies met the inclusion criteria for comparative analysis of patient demographics, treatment modalities, and outcomes.</p><p><strong>Results: </strong>A total of 35 studies, encompassing 35 patients with giant renal artery aneurysms, were included. The mean age was 53 years (15-88 years). Endovascular therapy was performed in 12 cases, while 20 patients underwent surgical management; 2 patients received combined treatment and 1 was treated conservatively. Overall, symptom improvement and complication profiles were reported descriptively across both surgical and endovascular treatments.</p><p><strong>Conclusion: </strong>Managing giant renal artery aneurysms necessitates a personalized, multifaceted approach. Intravascular therapy represents a feasible and minimally invasive option for selected patients with suitable anatomical structures and stable hemodynamics, while open surgery remains indispensable for complex anatomy or rupture. A multidisciplinary approach, guided by precise assessment of aneurysm morphology and renal function, is essential for optimal outcomes.</p>","PeriodicalId":72163,"journal":{"name":"American journal of clinical and experimental immunology","volume":"15 1","pages":"1-13"},"PeriodicalIF":1.3,"publicationDate":"2026-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13000732/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147500810","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Expert consensus on acupuncture for diabetic foot.","authors":"Xuexi Tang, Guoyan Li, Gang Wang, Sheng Chen, Li Zhang","doi":"10.62347/UQMI4547","DOIUrl":"10.62347/UQMI4547","url":null,"abstract":"<p><p>Diabetic foot (DF), is called \"foot gangrene\" (gangrene) or \"nerve gangrene\" (gangrene of the nerve area) in traditional Chinese medicine. It is a severe complication of diabetes, whose incidence rate is high, and the consequences is serious. Acupuncture is a promising therapy, it is effective, it can alleviate symptoms, accelerate the wound healing and reduce the risk of amputation. This consensus includes clinical evidence and expert practical experience, it shows acupuncture is an effective supportive treatment methods. Its main purpose is to provide practical, standardized, and safe instructions for clinicians. It can promote the use of acupuncture in evidence-based treatment of diabetic foot ulcers. The innovation points of this consensus are: 1. Stage guidance: It includes the indications, contraindications and Wagner classification system, which adjusts the treatment measures for different conditions. 2. Integrated diagnosis: It includes modern vascular assessment, neurological examinations, and TCM syndrome, such as ankle-brachial index, arterial oxygen partial pressure and nerve conduction studies, finally formulating different treatment plans. 3. Focus on strict operating procedures: Formulating safe and controlling infection measures for patients with diabetic foot to conduct acupuncture treatment, and figuring out the risk factors.</p>","PeriodicalId":72163,"journal":{"name":"American journal of clinical and experimental immunology","volume":"15 1","pages":"28-36"},"PeriodicalIF":1.3,"publicationDate":"2026-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13000733/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147500836","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Advances in the research and application of stem cell therapies for idiopathic pulmonary fibrosis.","authors":"Luyao Xu, Xinyang Hou, Xiumin Zhou, Meng Jiang","doi":"10.62347/GLJG9463","DOIUrl":"10.62347/GLJG9463","url":null,"abstract":"<p><p>Idiopathic pulmonary fibrosis (IPF) is a progressive, fatal lung disease primarily affecting the elderly, marked by lung tissue scarring and impaired function. Current treatments, such as pirfenidone and nintedanib, slow disease progression but do not halt it and are associated with side effects. Lung transplantation is limited by donor shortages and surgical risks. Stem cell-based therapies, particularly mesenchymal stromal cells (MSCs) from bone marrow, adipose tissue, and umbilical cord, offer promise due to their low immunogenicity, homing capacity, and paracrine signaling. Preclinical models show that MSCs or their miRNA-bearing extracellular vehicles (EVs) can inhibit the TGFβ/Smad pathway, reprogram macrophage polarization, and promote tissue regeneration through anti-inflammatory and repair factors (e.g., IL-10, HGF, VEGF). Genetic modifications like CXCR4 overexpression may enhance MSC efficacy. Early clinical trials suggest favorable safety and preliminary efficacy, though long-term validation is needed. Additionally, alveolar type 2 (AT2) cells derived from induced pluripotent stem cells (iPSCs) and lung epithelial cells from embryonic stem cells (ESCs) offer potential for alveolar repair. Bioengineering advancements, including hydrogel scaffolds and 3D lung organoids, enhance stem cell retention and provide platforms for IPF research and drug screening. This review explores the therapeutic potential of stem cell therapies in IPF, integrating recent bioengineering developments and clinical prospects.</p>","PeriodicalId":72163,"journal":{"name":"American journal of clinical and experimental immunology","volume":"14 6","pages":"300-312"},"PeriodicalIF":1.3,"publicationDate":"2025-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12816817/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146020830","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Modes of action of traditional Chinese medicine for diabetic infertility: from molecular pathways to clinical evidence.","authors":"Huajun Bo, Wei Lu, Jingting Zhang, Bingqian Zhang, Tianjuan Wang, Hong Zhang, Yunsong Yang","doi":"10.62347/OFRR9616","DOIUrl":"10.62347/OFRR9616","url":null,"abstract":"<p><p>Diabetes-associated infertility results from interconnected immunometabolic, oxidative, inflammatory, and endocrine disturbances that impair reproductive function in both sexes. Conventional therapies address individual symptoms but often fail to target this systemic, immune-mediated complexity. This narrative review summarizes preclinical and clinical evidence on the role of Traditional Chinese Medicine (TCM) in managing diabetic infertility, with a focus on immune-endocrine interactions, cytokine modulation, and inflammatory signaling. TCM interventions - including single-herb extracts, multi-herb formulations, and non-pharmacological approaches such as acupuncture and mind-body interventions-enhance insulin sensitivity, suppress pro-inflammatory cascades (NF-κB, TNF-α, IL-6), and regulate key immunometabolic pathways such as PI3K/Akt and AMPK. Mechanistic studies have also demonstrated improved nitric oxide bioavailability, endothelial function, and mitochondrial protection in gametogenic cells. They further show stabilization of hypothalamic-pituitary-gonadal and immune signaling, along with modulation of the gut-microbiota-immune axis. These immunomodulatory effects contribute to better spermatogenesis, semen quality, ovulation, endometrial receptivity, implantation, and pregnancy outcomes, particularly in individuals with insulin resistance or polycystic ovary syndrome. Overall, TCM shows promise as an adjunctive immunomodulatory strategy for diabetic infertility, supported by preliminary evidence of reproductive benefits. However, current evidence remains limited, and well-designed multicenter, immunology-informed clinical trials are required to confirm its efficacy.</p>","PeriodicalId":72163,"journal":{"name":"American journal of clinical and experimental immunology","volume":"14 6","pages":"267-299"},"PeriodicalIF":1.3,"publicationDate":"2025-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12816813/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146020863","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dietary patterns, physical activity, and risk of urinary tract diseases: a two sample Mendelian randomization analysis.","authors":"Chenxuan Zhao, Fengying Deng, Junlan Qiu, Qinqin Gao, Ming Li","doi":"10.62347/JENN1267","DOIUrl":"10.62347/JENN1267","url":null,"abstract":"<p><strong>Background: </strong>Previous studies have found associations between dietary habits, physical activity (PA) and a variety of renal/urinary disorders. However, only a few studies have used Mendelian randomisation analyses to explore the causal relationship between dietary habits, physical activity and a range of renal/urinary diseases.</p><p><strong>Methods: </strong>The exposure and outcome datasets were sourced from the BioBank, FinnGen, and the NHGRI-EBI databases. The exposure dataset comprised of 20 dietary patterns and 4 PA modalities, while the outcome dataset included 19 renal/urological disorders. The primary methods employed for MR analyses were inverse variance weighted. Heterogeneity and multiplicity analyses were conducted to ensure the validity of the results.</p><p><strong>Results: </strong>In terms of dietary habits, studies have found that consumption of soya-based sweets reduces the risk of chronic kidney disease (CKD). Consumption of fresh fruits prevented benign adrenal tumours and immunoglobulin A nephropathy (IgA-N). Consumption of paneer helps to reduce the risk of developing type 2 diabetes (T2D) nephropathy and immunoglobulin A nephropathy (IgA-N). In addition, consumption of nuts is a protective factor against type 2 diabetic nephropathy. Consumption of nuts, lean fish and fatty fish reduces the incidence of acute tubulointerstitial nephritis (ATIN). Among various forms of physical activity, recreational hiking was inversely associated with IgA-N nephritis and T2D nephritis. Other physical activities, including swimming, cycling, fitness and bowling, also reduced the risk of developing IgA-N. In contrast, leisure screen time (LST) was considered a risk factor.</p><p><strong>Conclusion: </strong>This study suggests that a sensible diet and increased leisure time walking may prevent chronic kidney diseases such as chronic renal insufficiency, chronic renal failure, type 2 kidney disease and IgA nephropathy. This study deepens the understanding of the association between diet, physical activity and renal/urinary abnormalities and provides practical recommendations for reducing the risk of developing these diseases.</p>","PeriodicalId":72163,"journal":{"name":"American journal of clinical and experimental immunology","volume":"14 6","pages":"359-372"},"PeriodicalIF":1.3,"publicationDate":"2025-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12816814/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146020887","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Analysis of the expression of ARNTL2 and miR-204-5p and their correlation with clinical pathological features in NSCLC patients.","authors":"Shuying You, Na Li, Xiangbo Zeng, Lile Wang","doi":"10.62347/PYVK8552","DOIUrl":"10.62347/PYVK8552","url":null,"abstract":"<p><strong>Objective: </strong>To analyze the expression of Aryl Hydrocarbon Receptor Nuclear Translocator-Like 2 (ARNTL2) and miR-204-5p in non-small cell lung cancer (NSCLC) patients and their correlation with clinicopathological characteristics.</p><p><strong>Methods: </strong>Respiratory department cases from April 2020 to April 2022 were selected, and patients were divided into an NSCLC group (80 cases) and a non-NSCLC group (60 cases). The expression levels of ARNTL2 and miR-204-5p and the survival status were compared between the two groups. The predictive value of ARNTL2 and miR-204-5p for mortality in NSCLC patients was analyzed.</p><p><strong>Results: </strong>TCGA data showed ARNTL2 expression was significantly higher and hsa-miR-204-5p significantly lower in cancer versus normal tissues (P<0.05). Patients with high ARNTL2 or miR-204-5p expression had shorter survival than those with low expression (P<0.05). In NSCLC patients, ARNTL2 was elevated and miR-204-5p reduced compared to non-NSCLC (P<0.05). High ARNTL2 or low miR-204-5p expression correlated with older age, larger tumor size, higher malignancy, lymph node metastasis, advanced stage, and smoking history (P<0.05). Over 36 months, survival was lower with high ARNTL2 but higher with high miR-204-5p (P<0.05). Pearson analysis showed ARNTL2 positively and miR-204-5p negatively correlated with mortality (P<0.05). ROC analysis yielded AUCs, sensitivities, and specificities of 0.914/86.7%/86.2% for ARNTL2, 0.934/81.7%/96.2% for miR-204-5p, and 0.920/89.8%/97.7% for combined detection.</p><p><strong>Conclusion: </strong>The expression levels of ARNTL2 and miR-204-5p in NSCLC are closely associated with patient age, tumor differentiation, and lymph node metastasis, and they have high predictive value for NSCLC-related mortality.</p>","PeriodicalId":72163,"journal":{"name":"American journal of clinical and experimental immunology","volume":"14 6","pages":"348-358"},"PeriodicalIF":1.3,"publicationDate":"2025-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12816815/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146020810","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Causal effects and metabolite mediation of immune cells in preterm birth: a Mendelian randomization study.","authors":"Tong Zhou, Yanqiu Zhang, Sheng Zhang, Jun Cao, Bin Feng, Jieyu Jin, Qingqin Tang, Jun Qiu, Longwei Qiao, Yuting Liang","doi":"10.62347/FJLL4103","DOIUrl":"10.62347/FJLL4103","url":null,"abstract":"<p><strong>Background: </strong>Preterm birth poses significant risks to neonatal health. Although immune dysregulation has been implicated in its etiology, the causal roles of specific immune cell phenotypes and the potential mediating effects of metabolites remain unclear. This study applied Mendelian randomization (MR) to investigate causal relationships between immune cell phenotypes and preterm birth, and to assess whether plasma metabolites mediate these associations.</p><p><strong>Methods: </strong>Two-sample and mediation MR analyses were performed using genetic variants from genome-wide association studies (GWAS) of immune cells and plasma metabolites. Causal estimates were primarily derived using inverse variance weighting (IVW), with sensitivity analyses conducted via MR-Egger, MR-PRESSO, and leave-one-out validation.</p><p><strong>Results: </strong>A total of 28 immune cell phenotypes and 47 metabolites were robustly associated with preterm birth (P < 0.05). Reverse MR analysis revealed no evidence of reverse causality for the identified immune phenotypes. Among these, CD28^- CD8^br AC exhibited the strongest association with increased preterm birth risk. Mediation analysis demonstrated that the effect of CD28^- CD8^br AC on preterm birth (total effect: 0.148; IVW OR [95% CI]: 1.160 [1.056-1.274], P = 0.002) was partially mediated by isoleucine levels (mediation proportion: 6.79%; P = 0.027) and the acetylcarnitine-to-propionylcarnitine (C2/C3) ratio (mediation proportion: 7.35%; P = 0.029). Sensitivity analyses confirmed the robustness of these findings.</p><p><strong>Conclusion: </strong>This study establishes causal links between immune cell phenotypes, metabolites, and genetic susceptibility to preterm birth. Specifically, CD28^- CD8^br AC may elevate preterm birth risk through modulation of isoleucine and the C2/C3 ratio, providing novel insights into disease mechanisms and potential therapeutic targets.</p>","PeriodicalId":72163,"journal":{"name":"American journal of clinical and experimental immunology","volume":"14 6","pages":"332-347"},"PeriodicalIF":1.3,"publicationDate":"2025-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12816816/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146020867","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Meta-analysis of the sedative effects of midazolam and dexmedetomidine in patients undergoing bronchoscopy.","authors":"Chunchu Kong, Lile Wang, Ting Zhong, Fan Deng, Fuxiu Zhang","doi":"10.62347/ISQD1848","DOIUrl":"10.62347/ISQD1848","url":null,"abstract":"<p><strong>Objective: </strong>To perform a meta-analysis on the sedative effects of midazolam and dexmedetomidine in patients undergoing bronchoscopy.</p><p><strong>Methods: </strong>Relevant literature on the sedative effects of midazolam and dexmedetomidine in patients undergoing bronchoscopy was searched in both Chinese and English databases.</p><p><strong>Results: </strong>A total of 19 studies published between 2012 and 2024 were included, involving 38 groups and 2,339 patients. Meta-analysis of continuous variables from fifteen studies reported no statistically significant difference in systolic blood pressure between the study group and the control group (MD = -0.27, 95% CI: -2.16 to 1.61, Z = -0.28, P = 0.78). Similarly, eight studies showed no significant difference in heart rate between the study group and the control group (MD = -0.62, 95% CI: -2.67 to 1.43, Z = -0.59, P = 0.55). Twelve studies demonstrated significantly higher oxygen saturation (SaO2) levels in the study group compared to the control group (MD = 1.88, 95% CI: 0.56 to 3.20, Z = 2.79, P = 0.01). Nine studies indicated that sedation satisfaction was significantly higher in the study group than in the control group (MD = 2.93, 95% CI: 1.16 to 4.70, Z = 3.25, P < 0.01). Ten studies assessed sedation scores, showing no statistically significant difference between groups (MD = 0.32, 95% CI: -0.02 to 0.67, Z = 1.82, P = 0.07). Awakening time, reported in eight studies, also showed no significant difference (MD = -2.70, 95% CI: -5.50 to 0.09, Z = -1.89, P = 0.06). Six studies reported VAS (Visual Analogue Scale) scores, showing a statistically significant difference (MD = -0.46, 95% CI: -0.83 to -0.08, Z = -2.39, P = 0.02). Meta-analysis of dichotomous variables from fourteen studies showed no significant difference in the incidence of adverse events between the groups (OR = -0.10, 95% CI: -0.49 to 0.29, Z = -0.49, P = 0.62). Meta-regression analysis suggested that heterogeneity mainly originated from differences in study type and methodology (P < 0.05).</p><p><strong>Conclusion: </strong>Both midazolam and dexmedetomidine demonstrate good sedative effects during bronchoscopy, and their use should be tailored to individual patient conditions.</p>","PeriodicalId":72163,"journal":{"name":"American journal of clinical and experimental immunology","volume":"14 6","pages":"313-331"},"PeriodicalIF":1.3,"publicationDate":"2025-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12816812/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146020870","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Granzyme B-producing B cells: a bidirectional relationship with breast cancer cells and implications for immunotherapy.","authors":"Hosein Hakimi, Fereshteh Mehdipour, Morteza Samadi, Sima Balouchi Anaraki, Reza Rasolmali, Abdol-Rasoul Talei, Abbas Ghaderi","doi":"10.62347/ANSN3150","DOIUrl":"10.62347/ANSN3150","url":null,"abstract":"<p><p>Granzyme B (GrB)-producing B cells have dual roles in tumor immunity, either killing tumor cells or suppressing antitumor responses by eliminating effector T cells. In this study, we aimed to investigate how breast cancer cells influence GrB-producing B cells from tumor-draining lymph nodes and whether B cell activation enhances their cytotoxic potential. Mononuclear cells were isolated from 14 fresh axillary lymph node samples by density gradient centrifugation using Ficoll-Hypaque. Lymphocytes were co-cultured with breast tumor cell lines (MCF-7 and MDA-231) in the presence of recombinant interleukin-21 (rIL-21) and anti-B cell receptor (BCR). B cell granzyme B production was measured by flow cytometry, while tumor cell (MCF-7) apoptosis was assessed using calcein AM release assays. Direct co-culture of lymphocytes with MCF-7 or MDA-MB-231 significantly reduced the frequency of GrB-producing B cells (P=0.001 and P=0.031, respectively), while tumor supernatants alone had no effect. When B cells were pre-stimulated with IL-21 and anti-BCR for 24 hours before direct co-culture, GrB expression was maintained at baseline levels (no significant difference vs. control). Additionally, B cells activated with IL-21 and anti-BCR caused significant apoptosis in MCF-7 cells (38±8.9%, P=0.023). In conclusion, breast cancer cells suppress GrB⁺ B cell responses via direct contact, but this suppression is reversible through B cell activation. Importantly, pre-activated B cells exhibit direct cytotoxic activity against tumor cells, highlighting their potential as an effector population for breast cancer immunotherapy.</p>","PeriodicalId":72163,"journal":{"name":"American journal of clinical and experimental immunology","volume":"14 5","pages":"241-249"},"PeriodicalIF":1.3,"publicationDate":"2025-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12629947/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145589978","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}