Iranian Journal of Immunology最新文献

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Low-dose Radiation Improves Tumor Immune Microenvironment, Enhancing the Effects of Anti-CTLA-4 Therapy.
IF 1.1 4区 医学
Iranian Journal of Immunology Pub Date : 2025-03-10 DOI: 10.22034/iji.2025.103258.2825
Jigang Dong, Ying Qi, Sha Sha
{"title":"Low-dose Radiation Improves Tumor Immune Microenvironment, Enhancing the Effects of Anti-CTLA-4 Therapy.","authors":"Jigang Dong, Ying Qi, Sha Sha","doi":"10.22034/iji.2025.103258.2825","DOIUrl":"10.22034/iji.2025.103258.2825","url":null,"abstract":"<p><strong>Background: </strong>Radiotherapy destroys tumor cells primarily through direct DNA damage by high-energy particles or indirect DNA damage by free radicals. High-dose radiotherapy (HDR) destroys tumor cells while also damaging normal cells and may potentially cause immunosuppression. The effect of low-dose radiotherapy (LDR) on the tumor microenvironment (TME) may differ from those of HDR.</p><p><strong>Objective: </strong>To determine if combining low-dose radiotherapy with immune checkpoint inhibitors results in synergistic effects.</p><p><strong>Methods: </strong>We established a mouse model for lung cancer and categorized mice into 4 cohorts: NC (negative control) cohort, LDR cohort, anti-CTLA-4 cohort, and LDR+anti-CTLA-4 cohort. Changes in tumor volume were observed in each group, with particular attention given to the variations in immune cells and cytokines within the mouse tumors following LDR.</p><p><strong>Results: </strong>The mice in the LDR+anti-CTLA-4 group exhibited the slowest growth in tumor volume, and low-dose radiotherapy tended to inhibit tumor growth. The proportion of infiltrating CD8+T cells increased and the proportion of infiltrating Treg cells decreased in the tumor after LDR. The levels of interferon (IFN) and the chemokines CXCL9, CXCL10 and CXCL11 were increased after low-dose radiotherapy.</p><p><strong>Conclusion: </strong>LDR has the ability to alter the immune microenvironment of tumors by promoting the production of IFN. Additionally, when combined with anti-CTLA-4, whole-body LDR can effectively suppress tumor growth in mice. The finding is of potential clinical significance and deserves further exploration.</p>","PeriodicalId":54921,"journal":{"name":"Iranian Journal of Immunology","volume":"22 1","pages":""},"PeriodicalIF":1.1,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143588314","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
Interaction Between Tfh/Tfr Ratio and Regulatory B Cell in Autoimmune Diseases.
IF 1.1 4区 医学
Iranian Journal of Immunology Pub Date : 2025-03-09 DOI: 10.22034/iji.2025.103848.2859
Chunhong Zhu, Xiaoying Ni, Jiangming Xu, Hao Wang, Hongqiang Shen
{"title":"Interaction Between Tfh/Tfr Ratio and Regulatory B Cell in Autoimmune Diseases.","authors":"Chunhong Zhu, Xiaoying Ni, Jiangming Xu, Hao Wang, Hongqiang Shen","doi":"10.22034/iji.2025.103848.2859","DOIUrl":"https://doi.org/10.22034/iji.2025.103848.2859","url":null,"abstract":"<p><p>The balance between follicular helper T cells (Tfh) and follicular regulatory T cells (Tfr) is crucial for maintaining immune tolerance. Tfh cells are key in producing autoantibodies by providing essential help to germinal center (GC) B cells, while Tfr cells prevent autoimmune inflammatory processes by controling Tfh responses. However, the signals that regulate Tfh and Tfr cells are largely unknown. Due to dysregulated Tfr/Tfh balance and autoantibody production, regulatory B cells (Bregs) have emerged as a key checkpoint in the GC response. Bregs are B cells with immunosuppressive capabilities. Significant advancements have been made in understanding the roles of Bregs, particularly their capacity to produce cytokines with anti-inflammatory properties and regulate Th17, Th1, and regulatory T cells (Tregs) in the context of autoimmune conditions. Bregs also play a pivotal role in shaping the development, regulation, and localization of Tfh and Tfr cells within the immune environment. Consequently, gaining mechanistic knowledge about the interactions between Tfh-Bregs and Tfr-Bregs has the potential to establish homeostasis and suppress the development of autoantibodies in a various disorders. Within the context of autoimmune disorders, this article provides a concise summary of the dysregulation of Tfh/Tfr, highlighting the critical role of Bregs in regulating this balance. The previously unrecognized interplay between Bregs and Tfh/Tfr cells will serve as an essential basis for the comprehension and management of autoimmune illnesses. It also promises to offer invaluable knowledge of the biological mechanisms of autoantibody synthesis.</p>","PeriodicalId":54921,"journal":{"name":"Iranian Journal of Immunology","volume":"22 1","pages":""},"PeriodicalIF":1.1,"publicationDate":"2025-03-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143588313","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
circ_0001006 Promotes Immune Escape in Non-small Cell Lung Cancer by Regulating the miR-320a/PD-L1 Axis.
IF 1.1 4区 医学
Iranian Journal of Immunology Pub Date : 2025-03-08 DOI: 10.22034/iji.2025.102661.2792
Zhenying Geng, Guoqing Zhang
{"title":"circ_0001006 Promotes Immune Escape in Non-small Cell Lung Cancer by Regulating the miR-320a/PD-L1 Axis.","authors":"Zhenying Geng, Guoqing Zhang","doi":"10.22034/iji.2025.102661.2792","DOIUrl":"https://doi.org/10.22034/iji.2025.102661.2792","url":null,"abstract":"<p><strong>Background: </strong>Circular RNAs are involved in the tumorigenesis of various tumors, including Non-small cell lung cancer (NSCLC).</p><p><strong>Objective: </strong>To investigate the expression of circ_0001006 in patients with NSCLC and its role in tumorigenesis and immune escape.</p><p><strong>Methods: </strong>A total of 115 patients with NSCLC were enrolled in the study. The expression of circ_0001006 and PD-L1 mRNA were detected using RT-qPCR. Cell proliferation activity, cell migration and invasion abilities were measured using the CCK-8 assay and Transwell chambers assay. Coculture of NSCLC cells with CD8 cytotoxic T cells was conducted to measure the levels of INF-γ, TNF-α, IL-2, and lactate dehydrogenase release in culture supernatants. Bioinformatic analysis was used to predict the target relevance among circ_0001006, miR-320a, and PD-L1.</p><p><strong>Results: </strong>The circ_0001006 and PD-L1 mRNA levels were elevated in NSCLC tissues and cells. Patients with high levels of circ_0001006 had a shorter overall survival rate. Inhibiting circ_0001006 reduced the proliferation, migration, and invasion of NSCLC cells, while increasing PD-L1 partially counteracting the inhibitory effects of si-circ_0001006. The co-culture system of NSCLC and CD8+ T cell was found to reduce the viability of activated CD8+ T cell when circ_0001006 is present. Knocking down circ_0001006 in co-culture cells led to an increase in the expression of INF-γ, TNF-α, and IL-2. The ability of si-circ_0001006 to enhance the activation of CD8+ T cells was diminished when PD-L1 was overexpressed.</p><p><strong>Conclusion: </strong>circ_0001006 may serve as a potential prognostic predictor and therapeutic target for NSCLC. Additionally, it offers insight into a novel regulatory mechanism of circ_0001006.</p>","PeriodicalId":54921,"journal":{"name":"Iranian Journal of Immunology","volume":"22 1","pages":""},"PeriodicalIF":1.1,"publicationDate":"2025-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143588312","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.
IF 1.1 4区 医学
Iranian Journal of Immunology Pub Date : 2025-03-05 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":"https://doi.org/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":""},"PeriodicalIF":1.1,"publicationDate":"2025-03-05","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
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
{"title":"Blood Cytokine Profile in Breast Cancer: Focusing on Differences among Molecular Subtypes.","authors":"Anil Demir, Husnu Sevik, Mert Guler, Furkan Turkoglu, Coskun Cakir, Mert Mahsuni Sevinc, Erdem Kinaci, Ufuk Oguz Idiz","doi":"10.22034/iji.2024.103582.2848","DOIUrl":"10.22034/iji.2024.103582.2848","url":null,"abstract":"<p><strong>Background: </strong>Breast cancer is the leading cause of cancer-related deaths in women. Cytokines have been linked to various cancers, and both benign and malignant breast diseases are associated with inflammation. However, there is limited understanding of how the immune system's cytokine response varies among different subtypes of breast cancer.</p><p><strong>Objective: </strong>To assess cytokine levels in breast cancer patients according to their subtypes and investigate the potential role of these cytokines in treatment.</p><p><strong>Methods: </strong>Patients with stage 1-2 breast cancer and healthy volunteers were included in the study. The breast cancer patients were classified as luminal A, luminal B, and triple negative based on ER, PR, HER2 receptor status, and Ki67 score of trucut biopsy results. Multiplex assay and flow cytometry were used to quantify the concentrations of IL-1β, IFN-α2, IFN-γ, TNF-α, MCP-1, IL-6, IL-8, IL-10, IL-12p (p70), IL-17A, IL-18, IL-23, and IL-33 in serum samples collected from all participants. Age, menopausal status, and hematologic parameters were also compared between groups.</p><p><strong>Results: </strong>The study involved 19 luminal A, 20 luminal B, 18 triple-negative patients and 21 healthy volunteers. TNF-α, IL-6, IL-8, IL-10, IL-12p (p70), IL-18, and IL-23 cytokines were significantly higher in breast cancer patients than in healthy volunteers. Significant differences in IFN-γ, IL-6, IL-8, IL-10, IL-12p (p70), IL-17A, IL-18, and IL-23 were observed between subtypes, with triple-negative patients showing lower cytokine levels, except for MCP-1.</p><p><strong>Conclusion: </strong>The decreased levels of cytokines in triple-negative breast cancer indicate lower immunogenicity leading to more aggressive tumor progression as a result of an insufficient immune response.</p>","PeriodicalId":54921,"journal":{"name":"Iranian Journal of Immunology","volume":"21 4","pages":"316-327"},"PeriodicalIF":1.1,"publicationDate":"2024-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142886489","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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