Iranian Journal of Immunology最新文献

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Immunogenetic Interplay of IL-6 and IL-6R Genes Variants and Circulating IL-6 Levels in ‎Toxoplasma gondii-infected Women with Recurrent Pregnancy Loss. IL-6和IL-6R基因变异与循环IL-6水平在刚地弓形虫感染复发性流产妇女中的免疫遗传学相互作用
IF 1.1 4区 医学
Iranian Journal of Immunology Pub Date : 2026-03-10 DOI: 10.22034/iji.2026.108627.3107
Muhammad Bar Khan, Sanaullah Khan, Muhammad Fawad Khan, Khair Rafiq, Muhammad Yaqoob, Muhammad Adnan
{"title":"Immunogenetic Interplay of IL-6 and IL-6R Genes Variants and Circulating IL-6 Levels in ‎Toxoplasma gondii-infected Women with Recurrent Pregnancy Loss.","authors":"Muhammad Bar Khan, Sanaullah Khan, Muhammad Fawad Khan, Khair Rafiq, Muhammad Yaqoob, Muhammad Adnan","doi":"10.22034/iji.2026.108627.3107","DOIUrl":"https://doi.org/10.22034/iji.2026.108627.3107","url":null,"abstract":"<p><strong>Background: </strong>Recurrent pregnancy loss (RPL) is a global health challenge in women. It has been reported that Toxoplasma gondii (T. gondii) infection and interleukin-6 (IL-6) bioavailability contribute to RPL.</p><p><strong>Objective: </strong>This study investigated IL-6 and IL-6 receptor (IL-6R) gene polymorphisms and blood IL-6 levels in T. gondii-infected women with RPL.</p><p><strong>Methods: </strong>The study comprised 163 women, including 83 infected (Group A: subgroups A1, A2) and 80 healthy (Group B). Demographic data, blood, and placental tissue samples were collected. The blood samples were screened for IL-6 levels through ELISA. DNA was extracted, and T. gondii-DNA was identified using PCR. IL-6 and IL-6R genes were amplified by PCR and sequenced using the Sanger method.</p><p><strong>Results: </strong>The IL-6 gene -174G/C (p=0.005) and -597G/A (p=0.0012) polymorphisms were significantly associated, while the -572G/C polymorphism was insignificantly associated (p=0.143) with infection and RPL. The mean blood IL-6 level was significantly variable across all groups (p < 0.001). The IL-6 gene -174GG and -597GG genotypes, and the IL-6R gene AA genotype, were common in Group-A2 (47.5%, 37.5%, 50%) and Group-B (56.2%, 60%, 68.8%), respectively, and were also significantly associated with elevated blood IL-6 levels. The -572GG genotype was common and was not significantly associated with elevated blood IL-6 levels across all groups (p=0.143). The IL-6 gene -174CC and -597AA genotypes and IL-6R gene CC genotype were highly prevalent in Group-A1 (48.8%, 41.9%, and 51.1%, respectively) and associated with low blood IL-6 levels.</p><p><strong>Conclusion: </strong>The IL-6 gene -174G/C, -597G/A, and IL-6R gene A/C polymorphisms play significant roles in RPL in women infected with T. gondii, and change IL-6 bioavailability.</p>","PeriodicalId":54921,"journal":{"name":"Iranian Journal of Immunology","volume":"23 1","pages":""},"PeriodicalIF":1.1,"publicationDate":"2026-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147391741","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Efficient Generation of Bone Marrow-Derived Murine Dendritic Cells: A Protocol ‎Optimization Study. 高效生成骨髓来源的小鼠树突状细胞:一项方案优化研究。
IF 1.1 4区 医学
Iranian Journal of Immunology Pub Date : 2026-03-10 DOI: 10.22034/iji.2026.108143.3086
Marziyeh Mousazadeh, Maryam Nikkhah, Negar Seyed, Sima Rafati, Saman Hosseinkhani
{"title":"Efficient Generation of Bone Marrow-Derived Murine Dendritic Cells: A Protocol ‎Optimization Study.","authors":"Marziyeh Mousazadeh, Maryam Nikkhah, Negar Seyed, Sima Rafati, Saman Hosseinkhani","doi":"10.22034/iji.2026.108143.3086","DOIUrl":"https://doi.org/10.22034/iji.2026.108143.3086","url":null,"abstract":"<p><strong>Background: </strong>Dendritic cells (DCs) are the most potent antigen-presenting cells, playing a central role in T cell activation and the stimulation of B cell antibody production. Owing to their immunological significance, DCs have been extensively explored for applications in cancer immunotherapy, dendritic cell-based vaccines, and strategies to overcome the immunosuppressive tumor microenvironment.</p><p><strong>Objective: </strong>Given the broad applications of DCs and the need for efficient generation protocols, the present study aimed to optimize key parameters influencing the production of bone marrow-derived dendritic cells (BMDCs).</p><p><strong>Methods: </strong>Variables such as mouse strain, cytokine concentrations, culture plate type, differentiation duration, incubation temperature, cell seeding density, and media replacement intervals were evaluated. CD11c expression was used as the primary marker to quantify BMDCs, while CD80 and CD86 were used as indicators of maturation status.</p><p><strong>Results: </strong>The optimized protocol yielded 60-70% CD11c+ BMDCs and 70-80% CD80/CD86 expression within 5 days.</p><p><strong>Conclusion: </strong>This robust and highly reproducible protocol offers valuable applications for in vitro dendritic cell generation studies.</p>","PeriodicalId":54921,"journal":{"name":"Iranian Journal of Immunology","volume":"23 1","pages":""},"PeriodicalIF":1.1,"publicationDate":"2026-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147391749","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
The Effect of Anti-TNF Group Drugs on Thyroid Function in Patients with ‎Rheumatoid Arthritis and Ankylosing Spondylitis. 抗tnf组药物对类风湿关节炎和强直性脊柱炎患者甲状腺功能的影响。
IF 1.1 4区 医学
Iranian Journal of Immunology Pub Date : 2026-03-10 DOI: 10.22034/iji.2026.107743.3081
Ismail Tuncekin, Murat Toprak
{"title":"The Effect of Anti-TNF Group Drugs on Thyroid Function in Patients with ‎Rheumatoid Arthritis and Ankylosing Spondylitis.","authors":"Ismail Tuncekin, Murat Toprak","doi":"10.22034/iji.2026.107743.3081","DOIUrl":"https://doi.org/10.22034/iji.2026.107743.3081","url":null,"abstract":"<p><strong>Background: </strong>Rheumatoid arthritis (RA) and ankylosing spondylitis (AS) are chronic autoimmune inflammatory disorders in which TNF-α plays a key role. Anti-TNF agents are widely used in the management of these diseases.</p><p><strong>Objective: </strong>Since TNF-α is also involved in the pathogenesis of autoimmune thyroid disease (AITD), this study aimed to assess whether anti-TNF therapy influences thyroid function.</p><p><strong>Methods: </strong>This prospective study included 50 RA and 51 AS patients aged 18-85 years. Patients received either conventional treatment (DMARDs and NSAIDs/sulfasalazine) or anti-TNF agents. Serum TSH, free T4, and anti-TPO levels were measured at baseline and after 6 months. Thyroid dysfunction and AITD prevalence were compared between the two treatment groups.</p><p><strong>Results: </strong>In the RA group, subclinical hyperthyroidism was observed in both arms; in the anti-TNF group, one patient had hypothyroidism, and another had subclinical hypothyroidism. Improvement in subclinical hyperthyroidism was observed in one patient in the DMARD arm, in one patient with hypothyroidism, and in one patient with subclinical hyperthyroidism in the anti-TNF arm (p>0.05). In the AS group, central hyperthyroidism developed in one patient receiving conventional treatment. In the anti-TNF group, one patient with subclinical hypothyroidism improved to normal values, while another developed central hypothyroidism. Anti-TPO positivity was 18% in the conventional group and 3.4% in the anti-TNF group (p>0.05). A significant TSH change was observed only in the RA-DMARD group (p < 0.05), while no significant changes in free T4 were detected in any group.</p><p><strong>Conclusion: </strong>Anti-TNF therapy showed no significant effect on thyroid function or autoimmune thyroid disease in patients with RA and AS during a six-month follow-up.</p>","PeriodicalId":54921,"journal":{"name":"Iranian Journal of Immunology","volume":"23 1","pages":""},"PeriodicalIF":1.1,"publicationDate":"2026-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147391796","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Investigating Autophagy Genes Expression and their Possible Relations with ‎Apoptosis in PBMCs of Patients with Thin Endometrium. 薄子宫内膜患者外周血细胞自噬基因表达及其与细胞凋亡关系的研究。
IF 1.1 4区 医学
Iranian Journal of Immunology Pub Date : 2026-03-10 DOI: 10.22034/iji.2026.109223.3128
Lida Aslanian-Kalkhoran, Mohammad Sadegh Soltani-Zangbar, Ali Aghebati-Maleki, Mahya AhmadpourYoushanlui, Mehdi Yousefi, Leili Aghebati Maleki
{"title":"Investigating Autophagy Genes Expression and their Possible Relations with ‎Apoptosis in PBMCs of Patients with Thin Endometrium.","authors":"Lida Aslanian-Kalkhoran, Mohammad Sadegh Soltani-Zangbar, Ali Aghebati-Maleki, Mahya AhmadpourYoushanlui, Mehdi Yousefi, Leili Aghebati Maleki","doi":"10.22034/iji.2026.109223.3128","DOIUrl":"https://doi.org/10.22034/iji.2026.109223.3128","url":null,"abstract":"<p><strong>Background: </strong>Autophagy genes are essential for proper uterine function, reproductive physiology, and the maintenance of endometrial atrophy (EA).</p><p><strong>Objective: </strong>This study aims to clarify how these genes impact endometrial thickness and their significance in the apoptosis of peripheral blood mononuclear cells (PBMCs) from patients with thin endometria.</p><p><strong>Methods: </strong>Blood samples were collected from 40 patients with a thin endometrium and 40 healthy controls, all in the non-pregnancy stage. Real-Time PCR was used to measure the expression levels of autophagy genes ATG5, ATG7, LC3B, Beclin1, FOXO1, FOXO3a, FOXO4, and FOXO6 in 40 women with thin endometrium and 40 healthy women. Apoptosis was also assessed by flow cytometry. To further elucidate the biological pathways and processes associated with the differentially expressed autophagy genes, we conducted a KEGG pathway enrichment analysis using the EnrichR tool.</p><p><strong>Results: </strong>Evaluation of autophagy gene expression showed a significant difference between the studied groups, with higher expression of ATG5, ATG7, LC3B, Beclin1, FOXO1, FOXO3a, FOXO4, and FOXO6 in the patient group. Moreover, there was a positive correlation between LC3B expression and the frequency of apoptotic cells in the studied patients. The EnrichR tool identified the enriched pathways: \"Shigellosis,\" \"FOXO signaling,\" \"Fruptosis,\" and, to a lesser extent, \"Longevity regulating pathway,\" \"Autophagy,\" and \"Mitophagy.\"</p><p><strong>Conclusion: </strong>Our results showed that autophagy genes associated with apoptosis in PBMCs may be involved in endometrial thinning in EA patients.</p>","PeriodicalId":54921,"journal":{"name":"Iranian Journal of Immunology","volume":"23 1","pages":""},"PeriodicalIF":1.1,"publicationDate":"2026-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147391815","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
The Relationship between Serum Interleukin-38 Levels and the Severity of ‎Coronary Artery Calcification: A Cross-Sectional Study. 血清白细胞介素-38水平与冠状动脉钙化严重程度的关系:一项横断面研究
IF 1.1 4区 医学
Iranian Journal of Immunology Pub Date : 2026-03-10 DOI: 10.22034/iji.2026.109116.3122
Mahsa Rostami, Mansour Moazenzadeh, Abdollah Jafarzadeh, Ahmad Shakeri, Parya Jangipour Afshar, Nazanin Zeinali, Hamidreza Rashidinejad
{"title":"The Relationship between Serum Interleukin-38 Levels and the Severity of ‎Coronary Artery Calcification: A Cross-Sectional Study.","authors":"Mahsa Rostami, Mansour Moazenzadeh, Abdollah Jafarzadeh, Ahmad Shakeri, Parya Jangipour Afshar, Nazanin Zeinali, Hamidreza Rashidinejad","doi":"10.22034/iji.2026.109116.3122","DOIUrl":"https://doi.org/10.22034/iji.2026.109116.3122","url":null,"abstract":"<p><strong>Background: </strong>Atherosclerosis is a chronic inflammatory, immune-mediated disease that is a leading cause of global mortality and disability. Coronary artery calcification (CAC) is a key predictor of the severity of coronary artery disease (CAD). Interleukin-38 (IL-38), a newly identified anti-inflammatory cytokine, may modulate inflammation and prevent atherosclerosis progression.</p><p><strong>Objective: </strong>This study aimed to evaluate the association between serum IL-38 levels and CAC severity among patients referred to the CT angiography unit at Razieh Firooz Hospital in Kerman City.</p><p><strong>Methods: </strong>In this cross-sectional study, 151 patients aged 50-70 years were evaluated. The mean age of the participants was 60.1 ± 6.9 years. CAC severity was determined using the Agatston scoring method and multi-detector CT scanners. Serum IL-38 levels were measured via enzyme-linked immunosorbent assay (ELISA). Statistical analyses were performed using an independent T-test and multivariable logistic regression.</p><p><strong>Results: </strong>Comparing serum IL-38 levels across CAC severity categories showed a statistically significant difference (P = 0.039). Mean serum IL-38 in patients with non-severe and severe calcification were 16.8 ± 5.5 pg/mL and 19.4 ± 4.9 pg/mL, respectively. However, in the multivariable regression analysis, adjusted for major risk factors including sex, age, diabetes, hypertension, and smoking, the association between serum IL-38 levels and CAC severity was not significant (P>0.05). In subgroup analyses, the significant association between IL-38 and CAC severity was observed only in older participants and in patients with established cardiovascular risk factors.</p><p><strong>Conclusion: </strong>Although serum IL-38 levels were higher in patients with severe CAC, this association did not remain significant after adjustment for major cardiovascular risk factors. Therefore, the observed elevation may reflect age- or risk-related inflammatory changes rather than a direct role of IL-38 in calcification. So, this relationship remains unclear. Further investigation is needed to clarify the potential context-dependent function of IL-38 in atherosclerosis progression.</p>","PeriodicalId":54921,"journal":{"name":"Iranian Journal of Immunology","volume":"23 1","pages":""},"PeriodicalIF":1.1,"publicationDate":"2026-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147391767","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Immunohistochemical Profiling of CD68 and VEGF in First-Trimester ‎Miscarriage Placentas. 早期妊娠流产胎盘中CD68和VEGF的免疫组化分析。
IF 1.1 4区 医学
Iranian Journal of Immunology Pub Date : 2026-03-10 DOI: 10.22034/iji.2026.109210.3127
Ghanyia Jasim Shanyoor, Mukhtar Khamis Haba, Ban Hadi Hameed
{"title":"Immunohistochemical Profiling of CD68 and VEGF in First-Trimester ‎Miscarriage Placentas.","authors":"Ghanyia Jasim Shanyoor, Mukhtar Khamis Haba, Ban Hadi Hameed","doi":"10.22034/iji.2026.109210.3127","DOIUrl":"https://doi.org/10.22034/iji.2026.109210.3127","url":null,"abstract":"<p><strong>Background: </strong>Miscarriage occurs when a pregnancy ends spontaneously before the fetus is viable outside the uterus. Early miscarriage, sometimes referred to as first-trimester miscarriage, happens before 12 weeks. Vascular endothelial growth factor (VEGF), an angiogenic protein essential for blood vessel formation, and cluster of differentiation 68 (CD68), a marker of macrophages, are vital to the immune response.</p><p><strong>Objective: </strong>This research aimed to evaluate VEGF and CD68 expression patterns in placental tissues and decidua from first-trimester miscarriage, to ascertain their potential roles in immune response and angiogenesis in miscarriage.</p><p><strong>Methods: </strong>The study included 60 women who experienced spontaneous abortion during the first trimester, 30 with missed abortion, and 30 with incomplete abortion. Using immunohistochemical staining, the expression of CD68 and VEGF in decidua and placental tissues was investigated. Expression levels were scored semi-quantitatively by averaging data from five fields per slide and subjected to statistical analysis.</p><p><strong>Results: </strong>Building on these methods, immunohistochemical staining confirmed significantly elevated CD68 expression in both placental and decidua tissues from missed and incomplete abortions, indicating enhanced macrophage infiltration. Widespread staining (>50%) was seen in 50% of incomplete abortion decidua and 30% of missed abortion tissues. In contrast, VEGF expression was predominantly negative across all samples, with no case showing positive staining, indicating impaired angiogenesis.</p><p><strong>Conclusion: </strong>The findings highlight a dual pathological mechanism in early miscarriage characterized by enhanced inflammatory macrophage infiltration and deficient angiogenic support. This imbalance may contribute to placental dysfunction and pregnancy failure. These results underscore the potential diagnostic and therapeutic relevance of immune-angiogenic pathways in early miscarriage.</p>","PeriodicalId":54921,"journal":{"name":"Iranian Journal of Immunology","volume":"23 1","pages":""},"PeriodicalIF":1.1,"publicationDate":"2026-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147391834","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
BATF Drives Cervical Cancer Progression and Immune Evasion by Regulating the STAT1-PD-L1 Axis. BATF通过调节STAT1-PD-L1轴驱动宫颈癌进展和免疫逃避。
IF 1.1 4区 医学
Iranian Journal of Immunology Pub Date : 2026-03-07 DOI: 10.22034/iji.2026.107285.3050
Jun Zhang, Yang Zhang, Jinwei Zhang
{"title":"BATF Drives Cervical Cancer Progression and Immune Evasion by Regulating the STAT1-PD-L1 Axis.","authors":"Jun Zhang, Yang Zhang, Jinwei Zhang","doi":"10.22034/iji.2026.107285.3050","DOIUrl":"10.22034/iji.2026.107285.3050","url":null,"abstract":"<p><strong>Background: </strong>Cervical cancer progression is driven by immune evasion mechanisms, including PD-L1-mediated suppression of T cell activity. BATF, a transcription factor, has been linked to tumor immunity; cancer remains incompletely understood.</p><p><strong>Objective: </strong>This study investigates the BATF-STAT1-PD-L1 axis in tumor progression and immune regulation.</p><p><strong>Methods: </strong>BATF expression was analyzed in cervical cancer tissues and cell lines. Functional assays assessed the impact of BATF knockdown on proliferation, apoptosis, autophagy, and migration. STAT1 regulation was examined via chromatin immunoprecipitation and Western blot. PD-L1 expression was measured by flow cytometry. In vivo xenograft models were used to evaluate tumor growth and response to PD-L1 blockade.</p><p><strong>Results: </strong>BATF was upregulated in cervical cancer and promoted tumor growth, metastasis, and immune evasion. BATF knockdown suppressed proliferation, enhanced apoptosis and autophagy, and reduced migration. Mechanistically, BATF transcriptionally activated STAT1, which induced PD-L1 expression. BATF suppression enhanced CD8⁺ T cell infiltration and improved the efficacy of PD-L1 blockade in vivo.</p><p><strong>Conclusion: </strong>BATF promotes cervical cancer progression by modulating STAT1 and PD-L1. Targeting BATF may enhance anti-tumor immunity and improve immunotherapy outcomes.</p>","PeriodicalId":54921,"journal":{"name":"Iranian Journal of Immunology","volume":"23 1","pages":""},"PeriodicalIF":1.1,"publicationDate":"2026-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147367233","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
MMP11 Promotes Immune Escape in Esophageal Carcinoma Cells via the PD-L1/c-MYC Signaling Pathway. MMP11通过PD-L1/c-MYC信号通路促进食管癌细胞免疫逃逸
IF 1.1 4区 医学
Iranian Journal of Immunology Pub Date : 2026-03-07 DOI: 10.22034/iji.2026.107483.3065
Xiaochen Wang, Yin Hong, Zhiheng Wang, Leilei Liu, Chen Zhang, Mingqiang Zhang, Yongyue Qian, Weiping Zhang, Zhang Shiyi
{"title":"MMP11 Promotes Immune Escape in Esophageal Carcinoma Cells via the PD-L1/c-MYC Signaling Pathway.","authors":"Xiaochen Wang, Yin Hong, Zhiheng Wang, Leilei Liu, Chen Zhang, Mingqiang Zhang, Yongyue Qian, Weiping Zhang, Zhang Shiyi","doi":"10.22034/iji.2026.107483.3065","DOIUrl":"10.22034/iji.2026.107483.3065","url":null,"abstract":"<p><strong>Background: </strong>Esophageal adenocarcinoma (ESCA) remains a highly malignant tumor with poor prognosis, partly due to immune escape mechanisms that promote tumor progression.</p><p><strong>Objective: </strong>This study aimed to investigate the role of matrix metalloproteinase 11 (MMP11) in regulating the programmed cell death ligand 1 (PD-L1)/cellular MYC (c-MYC) pathway and its effects on immune escape and tumor development in ESCA.</p><p><strong>Methods: </strong>MMP11 mRNA and protein levels were evaluated in ESCA tissues and cell lines (OE19 and OE33) using real-time quantitative polymerase chain reaction and Western blot analysis. Functional assays, including wound-healing and flow cytometry, were used to assess cell migration and apoptosis, respectively. Co-culture experiments using regulatory T cells and peripheral blood mononuclear cells were performed to analyze the proportions of immune cells. Key cytokines were measured, and a mouse xenograft model was used to validate in vivo effects.</p><p><strong>Results: </strong>MMP11 expression was significantly upregulated in ESCA tissues and cells. MMP11 knockdown inhibited PD-L1 expression, reduced ESCA cell migration, and promoted apoptosis. Additionally, MMP11 silencing downregulated proteins associated with the c-MYC pathway. Co-culture experiments revealed that MMP11 knockdown reduced the proportions of FoxP3+CD4+ and FoxP3+CD25+ cells while increasing FoxP3+CD8+ cells. Immunopromoting factors, including tumor necrosis factor alpha and interferon gamma, were elevated, whereas immunosuppressive factors, such as transforming growth factor beta and interleukin-10, decreased. In vivo, MMP11 knockdown suppressed tumor growth and reduced the expression of Ki-67, PD-L1, and c-MYC pathway proteins.</p><p><strong>Conclusion: </strong>MMP11 promotes ESCA progression by activating the PD-L1/c-MYC pathway and facilitating immune escape. Targeting MMP11 may enhance immunotherapeutic strategies for ESCA.</p>","PeriodicalId":54921,"journal":{"name":"Iranian Journal of Immunology","volume":"23 1","pages":""},"PeriodicalIF":1.1,"publicationDate":"2026-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147367251","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Antitumor Effects of Tumor-Derived Exosomes in Murine Hepatocellular Carcinoma Models. 肿瘤源性外泌体在小鼠肝癌模型中的抗肿瘤作用。
IF 1.1 4区 医学
Iranian Journal of Immunology Pub Date : 2025-12-23 DOI: 10.22034/iji.2025.106436.3025
Weibing Xu, Lulu Fan
{"title":"Antitumor Effects of Tumor-Derived Exosomes in Murine Hepatocellular Carcinoma Models.","authors":"Weibing Xu, Lulu Fan","doi":"10.22034/iji.2025.106436.3025","DOIUrl":"10.22034/iji.2025.106436.3025","url":null,"abstract":"<p><strong>Background: </strong>Exosomes (EXOs) are small vesicles derived from endosomes and secreted by most living cells including tumor cells. In recent years, these vesicles have been recognized as key mediators of intercellular communication, playing essential roles in the regulation and orchestration of diverse physiological and pathological processes within the organism.</p><p><strong>Objective: </strong>To further investigate hepatocellular carcinoma (HCC)-derived exosomes containing tumor-associated antigens and to evaluate their immunostimulatory capacity and antitumor effects using in vitro and in vivo approaches.</p><p><strong>Methods: </strong>Following isolation from tumor cells, exosomes were characterized and subsequently co-cultured with dendritic cells (DCs). The expression of surface molecules associated with DC maturation was then assessed using flow cytometry. A mouse liver cancer model was established and animals were randomly assigned to three groups: a negative control group (treated with PBS), an iDC group, and a DC-TEXs (tumor-derived exosomes) group. Tumor volume was monitored in all groups, with a focus on changes in immune cell populations and cytokine levels.</p><p><strong>Results: </strong>Our in vitro studies showed that Hepa1-6 cell-derived EXOs dose-dependently enhanced dendritic cell (DC) maturation, as evidenced by increased expression of surface MHC-II molecules, co-stimulatory markers (CD40, CD80, CD86), and the maturation marker CD83. In vivo studies using subcutaneous HCC mouse models demonstrated that TEX administration significantly alters the tumor immune microenvironment, mainly through increased T lymphocyte infiltration and proliferation.</p><p><strong>Conclusion: </strong>Our results suggest that TEXs can serve as endogenous immunotherapeutic agents by eliciting tumor-specific T lymphocyte responses through DC activation cascades. These findings provide novel insights into the therapeutic exploitation of tumor-derived vesicles for the treatment of hepatocellular carcinoma.</p>","PeriodicalId":54921,"journal":{"name":"Iranian Journal of Immunology","volume":"22 4","pages":"310-321"},"PeriodicalIF":1.1,"publicationDate":"2025-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145812376","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
In Vitro Expansion of Dendritic Cells Pulsed with Placental Peptides for the Generation of Antigen-Specific T Cells with Antitumor Activity. 胎盘肽脉冲树突状细胞体外扩增产生具有抗肿瘤活性的抗原特异性T细胞。
IF 1.1 4区 医学
Iranian Journal of Immunology Pub Date : 2025-12-21 DOI: 10.22034/iji.2025.107705.3075
Yu Lin, NengPing Huang, YuanBin He, PengJu Zuo, LiQiu Yang, FengJia Huang, YongQing Ye
{"title":"In Vitro Expansion of Dendritic Cells Pulsed with Placental Peptides for the Generation of Antigen-Specific T Cells with Antitumor Activity.","authors":"Yu Lin, NengPing Huang, YuanBin He, PengJu Zuo, LiQiu Yang, FengJia Huang, YongQing Ye","doi":"10.22034/iji.2025.107705.3075","DOIUrl":"10.22034/iji.2025.107705.3075","url":null,"abstract":"<p><strong>Background: </strong>Placental tissue contains a variety of tumor-associated antigens. Antigen-specific T cells generated by expanded dendritic cells (DCs) loaded with placental peptides have the potential to exert antitumor effects both in vitro and in vivo.</p><p><strong>Objective: </strong>To investigate the immunotherapeutic potential of placental peptides as a novel source of tumor-associated antigens (TAAs). We hypothesized that DCs, expanded and matured in vitro and pulsed with placental peptide extracts, can effectively prime antigen-specific T cells (ASTs) with robust cytotoxic activity against various tumor cell lines and in vivo tumor models.</p><p><strong>Methods: </strong>Mass spectrometry was used to identify tumor-related peptides within the placental extract. In vitro assays were employed to assess the expansion of DCs, their maturation following exposure to placental peptide preparations, and the subsequent activation of T cells.</p><p><strong>Results: </strong>The cytotoxic activity of ASTs was assessed and showed strong tumor cell killing across three cancer cell lines, U87MG (glioblastoma), SH-SY5Y (neuroblastoma), and MCF-7 (breast cancer). In a neuroblastoma animal model, ASTs treatment significantly reduced tumor proliferation, indicating substantial therapeutic potential in vivo.</p><p><strong>Conclusion: </strong>Our findings suggest that DCs pulsed with placental peptides can generate ASTs with potent antitumor activity in vitro and in vivo. Additional studies are needed to determine applicability across other tumor types, refine therapeutic parameters, and assess clinical potential.</p>","PeriodicalId":54921,"journal":{"name":"Iranian Journal of Immunology","volume":"22 4","pages":"284-298"},"PeriodicalIF":1.1,"publicationDate":"2025-12-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145800864","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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