Iranian Journal of Immunology最新文献

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MicroRNA-146a Inhibits Progression and Immune Evasion in Diffuse Large B-cell Lymphomas by Targeting Programmed Cell Death Ligand 1. MicroRNA-146a通过靶向程序性细胞死亡配体1抑制弥漫性大b细胞淋巴瘤的进展和免疫逃避
IF 1.1 4区 医学
Iranian Journal of Immunology Pub Date : 2025-03-30 DOI: 10.22034/iji.2025.104027.2874
Yan Li, Xiang Wang, Kuannv Yang
{"title":"MicroRNA-146a Inhibits Progression and Immune Evasion in Diffuse Large B-cell Lymphomas by Targeting Programmed Cell Death Ligand 1.","authors":"Yan Li, Xiang Wang, Kuannv Yang","doi":"10.22034/iji.2025.104027.2874","DOIUrl":"10.22034/iji.2025.104027.2874","url":null,"abstract":"<p><strong>Background: </strong>Earlier studies have highlighted the involvement of miRNA146a in tumor suppression indicating its potential to inhibit the progression of diffuse large B-cell lymphoma (DLBCL).</p><p><strong>Objective: </strong>To identify programmed death-ligand 1 (PD-L1) as a candidate for further research, as it plays a key role in regulating immune checkpoints in cancer and is associated with the involvement of miRNA146a in immune regulation and the response to inflammation.</p><p><strong>Methods: </strong>The expression of miR-146a and PD-L1 in DLBCL cells was detected using qPCR analysis. Subsequently, DLBCL cells (OCI-Ly-3 and OCI-Ly-7) were treated with either the miR-146a mimic or a blank plasmid. To assess immune evasion, DLBCL cells were cocultured with peripheral blood mononuclear cells, CD8+ T cells, or cytokine-induced killer cells. Furthermore, the target gene of miR-146a was predicted and validated.</p><p><strong>Results: </strong>Compared to the normal B-cell line (NCB), the level of miR-146a was significantly lower in DLBCL cells. Additionally, overexpression of miR-146a significantly reduced DLBCL viability, invasion, and immune evasion while simultaneously promoting apoptosis. Our findings also confirmed that miR-146a targeted PD-L1. Finally, the upregulation of PD-L1 notably reversed the tumor suppressive effects of miR-146a on DLBCL.</p><p><strong>Conclusion: </strong>Our study indicates that miR-146a inhibits the progression of DLBCL by enhancing antitumor immunity through the targeting of PD-L1. The therapeutic potential of this miRNA in lymphoma is highly desirable.</p>","PeriodicalId":54921,"journal":{"name":"Iranian Journal of Immunology","volume":"22 1","pages":"34-46"},"PeriodicalIF":1.1,"publicationDate":"2025-03-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143702371","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
Evaluation of Patients with Combined Immunodeficiency: A Single Center Experience. 联合免疫缺陷患者的评估:单中心经验。
IF 1.1 4区 医学
Iranian Journal of Immunology Pub Date : 2025-03-30 DOI: 10.22034/iji.2025.103499.2844
Hatice Firatoglu, Caner Aytekin, Figen Dogu, Sevgi Kostel Bal, Sule Haskologlu, Kaan Boztug, Aydan Ikinciogullari
{"title":"Evaluation of Patients with Combined Immunodeficiency: A Single Center Experience.","authors":"Hatice Firatoglu, Caner Aytekin, Figen Dogu, Sevgi Kostel Bal, Sule Haskologlu, Kaan Boztug, Aydan Ikinciogullari","doi":"10.22034/iji.2025.103499.2844","DOIUrl":"10.22034/iji.2025.103499.2844","url":null,"abstract":"<p><strong>Background: </strong>Severe combined immunodeficiency (SCID) is the most severe form of inborn errors of immunity (IEIs) and typically leads to death within the first year of life. Combined immunodeficiencies (CID) are immune disorders that are less severe than SCID and are characterized by qualitative or quantitative defects in T and B cells.</p><p><strong>Objective: </strong>To explore the clinical, laboratory, and genetic diagnostic approaches for patients diagnosed with SCID and CID.</p><p><strong>Methods: </strong>In this retrospective single-center study, we evaluated 54 patients diagnosed with SCID and CID between 2006 and 2019.</p><p><strong>Results: </strong>The male to female ratio was 30:24 and the rate of consanguinity was 77.8%. Among the patients, 23 were diagnosed with SCID and 31 diagnosed with CID. The most common phenotype in the SCID group was T-B-NK+ while in the CID group it was MHC class II deficiency. The median age at symptom onset for SCID and CID were 1 month and 5 months, respectively, while the median age at diagnosis was 4 months for SCID and 11 months for CID. The age at diagnosis of SCID and the age at diagnosis of symptoms were earlier than CID (p<0.05). Lymphopenia was present in 90.9% of patients with SCID and 51.6% of patients with CID (p<0.05). HSCT was performed in 10 out of 23 (43.4%) SCID patients and 10 out of 31 (32.2%) CID patients (total of 20 out of 54, 37%). The survival rates of SCID and CID patients who underwent HSCT were 80% and 70%, respectively.</p><p><strong>Conclusion: </strong>Consanguineous marriage, sibling death and family members with similar characteristics should be investigated for early diagnosis. Further investigations should be performed in the presence of lymphopenia. With the increasing number of genetic diagnosis facilities and HSCT centers, the survival rate of patients is expected to rise.</p>","PeriodicalId":54921,"journal":{"name":"Iranian Journal of Immunology","volume":"22 1","pages":"89-99"},"PeriodicalIF":1.1,"publicationDate":"2025-03-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143558805","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
Soluble HLA-E and Gastroesophageal Reflux Disease: A Novel Association‎. 可溶性 HLA-E 与胃食管反流病:一种新的关联
IF 1.1 4区 医学
Iranian Journal of Immunology Pub Date : 2025-03-30 DOI: 10.22034/iji.2025.104717.2915
Huda Saleem Hantoosh Hameed Al-Khalidy, Wafaa Hazim Salih, Batool Mutar Mahdi
{"title":"Soluble HLA-E and Gastroesophageal Reflux Disease: A Novel Association‎.","authors":"Huda Saleem Hantoosh Hameed Al-Khalidy, Wafaa Hazim Salih, Batool Mutar Mahdi","doi":"10.22034/iji.2025.104717.2915","DOIUrl":"10.22034/iji.2025.104717.2915","url":null,"abstract":"<p><strong>Background: </strong>Gastroesophageal reflux disease (GERD) is a prevalent clinical condition that affects millions ‎of individuals worldwide.‎.</p><p><strong>Objective‎: </strong>To assess the level of soluble HLA-E (sHLA-E) as a biomarker in the diagnosis and ‎immunopathogenesis of GERD patients.‎.</p><p><strong>Methods‎: </strong>The case-control prospective study included 40 GERD patients who were consulted at the ‎Gastroenterology Unit of Al-Kindy Teaching Hospital, as along with 40 healthy control ‎subjects. The study period extended from January 2023 to May 2024. Blood was drawn from ‎both groups and serum was separated to assesss HLA-E using a sandwich enzyme-linked ‎immunosorbent assay (ELISA) kit.‎.</p><p><strong>Results: </strong>There was a statistically significant difference in sHLA-E levels between GERD patients and ‎healthy controls (p = 0.021). The median sHLA-E level was significantly higher in GERD ‎patients (0.370 ng/mL) compared to controls (0.148 ng/mL). A receiver operating characteristic ‎‎(ROC) curve was generated to evaluate the diagnostic performance of soluble HLA-E (sHLA-E) ‎in predicting GERD. The area under the ROC curve (AUC) was calculated to assess the ‎discriminatory ability of sHLA-E, with a value of 0.649 (95% CI: 0.534-0.752, p = 0.021). The ‎optimal cutoff value for sHLA-E was determined to be ≤0.65 ng/mL, with a sensitivity of ‎‎85.1%, specificity of 27.3%, positive predictive value of 65.9%, negative predictive value of ‎‎69.4%, and accuracy of 35.0%.‎.</p><p><strong>Conclusion‎: </strong>The study provides evidence of an association between elevated sHLA-E levels and GERD. It ‎also suggests that sHLA-E has a moderate discriminatory ability as a biomarker in predicting ‎GERD.‎.</p>","PeriodicalId":54921,"journal":{"name":"Iranian Journal of Immunology","volume":"22 1","pages":"83-88"},"PeriodicalIF":1.1,"publicationDate":"2025-03-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143733285","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
Transmembrane TNF-α Reverse Signaling Alleviates Lipopolysaccharide-induced ‎Inflammation by Regulating the MCPIP1/SIRT1/NF-κB Pathway. 跨膜 TNF-α 反向信号通过调节 MCPIP1/SIRT1/NF-κB 通路缓解脂多糖诱发的炎症
IF 1.1 4区 医学
Iranian Journal of Immunology Pub Date : 2025-03-30 DOI: 10.22034/iji.2025.104371.2907
Chenxi Li, Mingxin Lin, Xiujuan Li, Lijin Chen, Yubin Lin, Huiming Ye
{"title":"Transmembrane TNF-α Reverse Signaling Alleviates Lipopolysaccharide-induced ‎Inflammation by Regulating the MCPIP1/SIRT1/NF-κB Pathway.","authors":"Chenxi Li, Mingxin Lin, Xiujuan Li, Lijin Chen, Yubin Lin, Huiming Ye","doi":"10.22034/iji.2025.104371.2907","DOIUrl":"10.22034/iji.2025.104371.2907","url":null,"abstract":"<p><strong>Background: </strong>Studies have demonstrated that transmembrane tumor necrosis factor-α (tmTNF-α) plays an anti-inflammatory role. tmTNF-α has a dual function, acting as both a signaling ligand and a receptor that transmits reverse signaling to cells expressing tmTNF-α. However, the role and mechanisms of tmTNF-α reverse signaling in sepsis are not fully understood.</p><p><strong>Objective‎: </strong>To explore the potential role and mechanisms of tmTNF-α reverse signaling in lipopolysaccharide (LPS)-induced inflammation.</p><p><strong>Methods‎: </strong>The expression levels of tmTNF-α and TNF-α mRNA were evaluated using flow cytometry and real-time PCR, respectively. We employed the anti-TNF-α drug infliximab to stimulate tmTNF-α reverse signaling and measured interleukin-6 (IL-6) and monocyte chemoattractant protein (MCP)-1 production through real-time PCR and ELISA in THP-1-derived macrophages. The location of p65 was determined through immunofluorescence assay. The phosphorylation and acetylation of p65, as well as the expression levels of MCP-induced protein 1 (MCPIP1) and Sirtuin 1 (SIRT1), were evaluated using western blotting.</p><p><strong>Results: </strong>Our findings revealed that tmTNF-α reverse signaling reduced the expression of IL-6 and MCP-1 triggered by LPS. tmTNF-α reverse signaling inhibited the nuclear translocation of p65, suppressed p65 phosphorylation and acetylation, and upregulated the expression of negative regulatory molecules MCPIP1 and SIRT1 in the LPS/ toll-like receptor 4 (TLR4) signaling pathway.</p><p><strong>Conclusion‎: </strong>This study demonstrates that tmTNF-α reverse signaling plays a negative regulatory role in inflammation triggered by LPS by inhibiting the TLR4/ nuclear factor kappa B (NF-κB) signaling pathway. This study helps to further understand the function of tmTNF-α reverse signaling and offers new therapeutic possibilities for sepsis and other inflammatory disease conditions.</p>","PeriodicalId":54921,"journal":{"name":"Iranian Journal of Immunology","volume":"22 1","pages":"13-24"},"PeriodicalIF":1.1,"publicationDate":"2025-03-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143733286","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
Analysis of the Blood Levels of NK and NKT Cells in Patients with Severe SARS-CoV-2 Infection. 重症SARS-CoV-2感染患者外周血NK、NKT细胞水平分析
IF 1.1 4区 医学
Iranian Journal of Immunology Pub Date : 2024-12-31 Epub Date: 2024-12-03 DOI: 10.22034/iji.2024.100817.2710
Marlen Vitales-Noyola, Diana Lorena Alvarado-Hernández, Raquel Sánchez-Gutiérrez, Berenice Hernández-Castro, Lourdes González-Baranda, Sofía Bernal-Silva, Andreu Comas-García, Carmen Sánchez-Torres, Roberto González-Amaro
{"title":"Analysis of the Blood Levels of NK and NKT Cells in Patients with Severe SARS-CoV-2 Infection.","authors":"Marlen Vitales-Noyola, Diana Lorena Alvarado-Hernández, Raquel Sánchez-Gutiérrez, Berenice Hernández-Castro, Lourdes González-Baranda, Sofía Bernal-Silva, Andreu Comas-García, Carmen Sánchez-Torres, Roberto González-Amaro","doi":"10.22034/iji.2024.100817.2710","DOIUrl":"10.22034/iji.2024.100817.2710","url":null,"abstract":"<p><strong>Background: </strong>Clinical features of SARS-CoV-2 infection vary, ranging from asymptomatic cases to pneumonia, and other serious complications. Some populations have been observed to be at higher risk for severe disease and death compared to other ethnical groups.</p><p><strong>Objective: </strong>To evaluate two parameters of the innate immune system, that play a significant role in viral immunity.</p><p><strong>Methods: </strong>In samples of peripheral blood from sixteen patients with severe COVID-19, ten with asymptomatic to mild illness, and fifteen healthy subjects, the percentage of NK and NKT cells, the expression of different NK cell receptors and the blood levels of pro-inflammatory cytokines were tested.</p><p><strong>Results: </strong>We observed that patients with severe COVID-19 showed significantly lower frequencies of both CD56dim and CD56bright NK cells compared to patients with mild illness or healthy controls. Furthermore, patients with severe manifestation of COVID-19 exhibited an aberrant expression of the natural cytotoxicity receptors NKp30, NKp44 and NKp46. Similarly, NK cells from these patients showed statistically significant differences in the expression of various killer immunoglobulin-like receptors (KIRs) in the two main cell subsets (CD56bright, CD56dim) compared to controls or patients with mild disease. Moreover, patients with severe illness displayed decreased frequency of NKT cells (defined as CD3+CD56+) and elevated blood levels of the cytokines IL-6 and IL-8.</p><p><strong>Conclusion: </strong>This study suggests that the abnormal features of NK and NKT cells observed in patients with severe SARS-CoV-2 infection may play an important role in the outcome of this infectious disease in various population groups.</p>","PeriodicalId":54921,"journal":{"name":"Iranian Journal of Immunology","volume":"21 4","pages":"340-352"},"PeriodicalIF":1.1,"publicationDate":"2024-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142774924","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
Effects of Intrauterine Infusion of G-CSF and HCG on Peripheral Blood Treg and Pregnancy Outcome in Patients with Thin Endometrium Undergoing Frozen-thawed Embryo Transfer. 子宫内输注G-CSF和HCG对薄子宫内膜冻融胚胎移植患者外周血Treg和妊娠结局的影响。
IF 1.1 4区 医学
Iranian Journal of Immunology Pub Date : 2024-12-31 Epub Date: 2024-12-10 DOI: 10.22034/iji.2024.103095.2815
Hui-Jun Yu, Qi Wan, Li Tan, Xing-Yu Lv
{"title":"Effects of Intrauterine Infusion of G-CSF and HCG on Peripheral Blood Treg and Pregnancy Outcome in Patients with Thin Endometrium Undergoing Frozen-thawed Embryo Transfer.","authors":"Hui-Jun Yu, Qi Wan, Li Tan, Xing-Yu Lv","doi":"10.22034/iji.2024.103095.2815","DOIUrl":"10.22034/iji.2024.103095.2815","url":null,"abstract":"<p><strong>Background: </strong>Patients with thin endometrium undergoing frozen-thawed embryo transfer often encounter challenges with pregnancy outcomes. Enhancing endometrial receptivity and immune tolerance may improve these outcomes.</p><p><strong>Objective: </strong>To investigate the effects of intrauterine perfusion of granulocyte colony-stimulating factor (G-CSF) and human chorionic gonadotropin (HCG) on regulatory T cells (Tregs) and pregnancy outcomes in patients with thin endometrium undergoing frozen-thawed embryo transfer.</p><p><strong>Methods: </strong>150 patients with thin endometrium were randomly assigned to three groups: a control group that received no intervention, an HCG group, and a G-CSF group. The effectiveness of the treatments was assessed by comparing uterine parameters, Treg levels, and pregnancy outcomes across the groups.</p><p><strong>Results: </strong>The HCG and G-CSF groups exhibited significant improvements compared to the control group, including increased endometrial thickness, enhanced blood flow, higher expression of endometrial receptivity markers (integrin αvβ3, osteopontin), and elevated Treg levels. Notably, the G-CSF group demonstrated even greater enhancements compared to the HCG group, with significantly higher endometrial thickness, better blood flow, increased receptivity markers, and elevated Treg levels. Additionally, the G-CSF group achieved significantly higher biochemical and clinical pregnancy rates compared to both the HCG and control groups. This highlights the potential of G-CSF in improving pregnancy outcomes for patients with a thin endometrium.</p><p><strong>Conclusion: </strong>The intrauterine perfusion of G-CSF significantly enhanced pregnancy outcomes in patients with thin endometrium by improving endometrial blood flow, immune tolerance, thickness, Treg induction, and embryo implantation. These findings suggest that G-CSF could be a promising therapeutic option for this patient population.</p>","PeriodicalId":54921,"journal":{"name":"Iranian Journal of Immunology","volume":"21 4","pages":"328-339"},"PeriodicalIF":1.1,"publicationDate":"2024-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142803467","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
Gamma-delta T Cells in Bladder Cancer Draining Lymph Nodes. 膀胱癌引流淋巴结中的γ-δ T 细胞
IF 1.1 4区 医学
Iranian Journal of Immunology Pub Date : 2024-12-31 Epub Date: 2024-11-23 DOI: 10.22034/iji.2024.103549.2846
Ali Ariafar, Zahra Mansourabadi, Hojat Alipoor, Zahra Faghih
{"title":"Gamma-delta T Cells in Bladder Cancer Draining Lymph Nodes.","authors":"Ali Ariafar, Zahra Mansourabadi, Hojat Alipoor, Zahra Faghih","doi":"10.22034/iji.2024.103549.2846","DOIUrl":"10.22034/iji.2024.103549.2846","url":null,"abstract":"<p><strong>Background: </strong>Gamma-delta (γδ) T cells are a distinct subset of T cells with a receptor composed of γ and δ chains. Their ability to directly recognize stress-induced molecules and non-peptide antigens expressed by cancer cells, along with their capacity to produce cytokines and interact with other immune cells, makes them potentially significant contributors to immune-based treatments.</p><p><strong>Objective: </strong>To investigate the presence and frequency of Tγδ cells in tumor-draining lymph nodes of patients with bladder cancer (BC), and to assess their association with prognostic parameters.</p><p><strong>Methods: </strong>Forty-nine fresh tumor-draining lymph nodes from untreated patients with BC were minced to obtain single cells. The cells were surface-stained with anti-CD3, anti-TCRγδ, and anti-HLA-DR antibodies, then acquired on a four-color FACSCalibur flow cytometer, and analyzed by FlowJo software.</p><p><strong>Results: </strong>On average, 2.07% ± 1.99% of CD3+ lymphocytes in regional nodes of BC exhibited a γδ T phenotype. A considerable percentage of these cells (37.90% ± 24.42%) expressed HLA-DR. Statistical analysis revealed that while the frequency of γδ T cells showed no variation among patients with different prognoses, the HLA-DR+ subset was higher in T4 patients than in T2 patients (p=0.031). These cells also tended to be increased in stage III compared to stage II (p=0.077).</p><p><strong>Conclusion: </strong>The data collectively indicated an association of HLA-DR expressing γδ T cells with prognostic factors related to tumor progression (higher T-group and stage), suggesting their potential involvement in disease progression. However, future research, including longitudinal studies with larger cohorts, needs to validate these findings and elucidate the functional roles of γδ T cells in the immune response against BC.</p>","PeriodicalId":54921,"journal":{"name":"Iranian Journal of Immunology","volume":"21 4","pages":"271-278"},"PeriodicalIF":1.1,"publicationDate":"2024-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142693817","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
Design and Cytotoxicity Evaluation of a Cancer-targeting Immunotoxin Based on a Camelid Nanobody-PE Fusion Protein. 基于骆驼纳米体- pe融合蛋白的肿瘤靶向免疫毒素的设计和细胞毒性评价。
IF 1.1 4区 医学
Iranian Journal of Immunology Pub Date : 2024-12-31 Epub Date: 2024-12-28 DOI: 10.22034/iji.2024.104052.2878
Mona Khoshbakht, Mohammad Mahdi Forghanifard, Hossein Aghamollaei, Jafar Amani
{"title":"Design and Cytotoxicity Evaluation of a Cancer-targeting Immunotoxin Based on a Camelid Nanobody-PE Fusion Protein.","authors":"Mona Khoshbakht, Mohammad Mahdi Forghanifard, Hossein Aghamollaei, Jafar Amani","doi":"10.22034/iji.2024.104052.2878","DOIUrl":"10.22034/iji.2024.104052.2878","url":null,"abstract":"<p><strong>Background: </strong>Developing effective targeted treatment approaches to overcome drug resistance remains a crucial goal in cancer research. Immunotoxins have dual functionality in cancer detection and targeted therapy.</p><p><strong>Objective: </strong>This study aimed to engineer a recombinant chimeric fusion protein by combining a nanobody-targeting domain with an exotoxin effector domain. The chimeric protein was designed to bind surface-expressed GRP78 on cancer cells, facilitating internalization and inducing apoptosis to inhibit proliferation and survival.</p><p><strong>Methods: </strong>Using a flexible linker, we designed two constructs linking VHH nanobody domains to Pseudomonas exotoxin (PE) domains II, III, and Ib. These constructs were then optimized for expression in E. coli BL21 (DE3) using the pET28a vector. Following the expression of the recombinant proteins, we purified them and tested their binding capability, cytotoxicity, and ability to induce apoptosis in breast cancer cell lines MDA-MB-231 and MCF-7, as well as in control cell lines HEK-293 and MDA-MB-468. The binding affinity was measured using a cell-based ELISA, internalization was assessed through Western blotting, cytotoxicity was evaluated by an MTT assay, and apoptosis was determined using flow cytometry with an Annexin V kit.</p><p><strong>Results: </strong>The immunotoxin specifically bound to cancer cells expressing csGRP78. The results of the cytotoxicity test showed that the cytotoxic effect of two constructs, I and II, depended on concentration and time. With an increase in both components, the effect of recombinant proteins also increased. Both constructs were able to penetrate and induce apoptosis in csGRP78+ cells.</p><p><strong>Conclusion: </strong>These immunotoxin structures showed therapeutic potential against GRP78-expressing cancers, making them suitable candidates for targeted therapy pending in vivo studies.</p>","PeriodicalId":54921,"journal":{"name":"Iranian Journal of Immunology","volume":"21 4","pages":"302-315"},"PeriodicalIF":1.1,"publicationDate":"2024-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142900532","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
Evaluation of Metastasis Inhibition by ABD-IL-2 Compared to Human IL-2 in a Breast Cancer Mouse Model. 与人IL-2相比,ABD-IL-2在乳腺癌小鼠模型中对转移抑制的评价
IF 1.1 4区 医学
Iranian Journal of Immunology Pub Date : 2024-12-31 Epub Date: 2024-12-08 DOI: 10.22034/iji.2024.103157.2819
Maryam Teimouri, Ahad Muhammadnejad, Mir Saeed Yekaninejad, Alireza Razavi, Gholam Ali Kardar
{"title":"Evaluation of Metastasis Inhibition by ABD-IL-2 Compared to Human IL-2 in a Breast Cancer Mouse Model.","authors":"Maryam Teimouri, Ahad Muhammadnejad, Mir Saeed Yekaninejad, Alireza Razavi, Gholam Ali Kardar","doi":"10.22034/iji.2024.103157.2819","DOIUrl":"10.22034/iji.2024.103157.2819","url":null,"abstract":"<p><strong>Background: </strong>Interleukin-2 (IL-2) is a well-known cytokine that plays a crucial role in stimulating immune cells, including natural killer (NK) cells and cytotoxic T cells. It has been studied as an immunotherapy for a variety of diseases, including cancer. However, due to its short serum half-life, high doses of IL-2 are required which can result in systemic toxicities like capillary leak syndrome.</p><p><strong>Objective: </strong>To demonstrate the enhanced antitumor efficacy of Albumin Binding Domain-conjugated IL-2 (ABD-IL-2) at a lower dose compared to IL-2.</p><p><strong>Methods: </strong>IL-2 and ABD-IL-2 were purified using Ni-NTA resin with a histidine sequence added to their C-terminal region for purification purpose. Peripheral blood lymphocytes were stimulated with IL-2 and ABD-IL-2 to assess their function. 4T1 cells were injected into BALB/c mice to establish a breast cancer model with metastasis evaluated in the lungs.</p><p><strong>Results: </strong>Both recombinant proteins significantly stimulated T lymphocyte proliferation compared to the negative control (P=0.000, P=0.001). Administration of both proteins reduced the size of isolated tumors in the breast cancer mouse model. The control group had more nodules and larger lung metastatic centers (P=0.000). Metastasis to secondary lymphoid organs occurred only in the control group.</p><p><strong>Conclusion: </strong>By using ABD-IL-2 at a one-third concentration compared to IL-2, we aimed to reduce administration toxicity associated with high doses of IL-2 in immunotherapy. This approach shows potential for improving IL-2-based treatments while minimizing adverse effects.</p>","PeriodicalId":54921,"journal":{"name":"Iranian Journal of Immunology","volume":"21 4","pages":"294-301"},"PeriodicalIF":1.1,"publicationDate":"2024-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142792744","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
Blood Cytokine Profile in Breast Cancer: Focusing on Differences among Molecular Subtypes. 乳腺癌血液细胞因子谱:关注分子亚型的差异。
IF 1.1 4区 医学
Iranian Journal of Immunology Pub Date : 2024-12-31 Epub Date: 2024-12-25 DOI: 10.22034/iji.2024.103582.2848
Anil Demir, Husnu Sevik, Mert Guler, Furkan Turkoglu, Coskun Cakir, Mert Mahsuni Sevinc, Erdem Kinaci, Ufuk Oguz Idiz
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