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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 Q4 IMMUNOLOGY Pub Date : 2025-03-10 DOI: 10.22034/iji.2025.103258.2825
Jigang Dong, Ying Qi, Sha Sha

Background: 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.

Objective: To determine if combining low-dose radiotherapy with immune checkpoint inhibitors results in synergistic effects.

Methods: 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.

Results: 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.

Conclusion: 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.

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引用次数: 0
Interaction Between Tfh/Tfr Ratio and Regulatory B Cell in Autoimmune Diseases.
IF 1.1 4区 医学 Q4 IMMUNOLOGY Pub Date : 2025-03-09 DOI: 10.22034/iji.2025.103848.2859
Chunhong Zhu, Xiaoying Ni, Jiangming Xu, Hao Wang, Hongqiang Shen

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.

{"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 Q4 IMMUNOLOGY Pub Date : 2025-03-08 DOI: 10.22034/iji.2025.102661.2792
Zhenying Geng, Guoqing Zhang

Background: Circular RNAs are involved in the tumorigenesis of various tumors, including Non-small cell lung cancer (NSCLC).

Objective: To investigate the expression of circ_0001006 in patients with NSCLC and its role in tumorigenesis and immune escape.

Methods: 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.

Results: 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.

Conclusion: 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.

{"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 Q4 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

Background: 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.

Objective: To explore the clinical, laboratory, and genetic diagnostic approaches for patients diagnosed with SCID and CID.

Methods: In this retrospective single-center study, we evaluated 54 patients diagnosed with SCID and CID between 2006 and 2019.

Results: 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.

Conclusion: 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.

{"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 Q4 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

Background: 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.

Objective: To evaluate two parameters of the innate immune system, that play a significant role in viral immunity.

Methods: 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.

Results: 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.

Conclusion: 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.

背景:SARS-CoV-2感染的临床特征各不相同,从无症状病例到肺炎,以及其他严重并发症。据观察,与其他族裔群体相比,一些人群患严重疾病和死亡的风险更高。目的:探讨在病毒免疫中起重要作用的先天免疫系统的两个参数。方法:对16例重症COVID-19患者、10例无症状至轻症患者和15例健康人的外周血进行NK、NKT细胞百分比、不同NK细胞受体表达及血中促炎因子水平的检测。结果:我们观察到,与轻症患者或健康对照组相比,重症COVID-19患者CD56dim和CD56bright NK细胞的频率均显著降低。此外,严重表现的COVID-19患者表现出天然细胞毒性受体NKp30、NKp44和NKp46的异常表达。同样,与对照组或轻度疾病患者相比,来自这些患者的NK细胞在两种主要细胞亚群(CD56bright, CD56dim)中各种杀伤免疫球蛋白样受体(KIRs)的表达具有统计学显著差异。此外,病情严重的患者表现出NKT细胞(定义为CD3+CD56+)的频率降低和细胞因子IL-6和IL-8的血液水平升高。结论:本研究提示在SARS-CoV-2重症感染患者中观察到的NK和NKT细胞的异常特征可能在不同人群中该传染病的转归中起重要作用。
{"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 Q4 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

Background: 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.

Objective: 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.

Methods: 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.

Results: 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.

Conclusion: 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.

背景:子宫内膜薄的患者在接受冻融胚胎移植时经常遇到妊娠结局的挑战。增强子宫内膜容受性和免疫耐受可能改善这些结果。目的:探讨子宫内灌注粒细胞集落刺激因子(G-CSF)和人绒毛膜促性腺激素(HCG)对薄子宫内膜冻融胚胎移植患者调节性T细胞(Tregs)和妊娠结局的影响。方法:将150例薄子宫内膜患者随机分为3组:不进行干预的对照组、HCG组和G-CSF组。通过比较各组的子宫参数、Treg水平和妊娠结局来评估治疗的有效性。结果:与对照组相比,HCG和G-CSF组表现出显著改善,包括子宫内膜厚度增加,血流量增加,子宫内膜容受性标志物(整合素αvβ3,骨桥蛋白)表达增加,Treg水平升高。值得注意的是,与HCG组相比,G-CSF组表现出更大的增强,子宫内膜厚度明显增加,血流更好,接受性标志物增加,Treg水平升高。此外,与HCG和对照组相比,G-CSF组取得了显著更高的生化和临床妊娠率。这突出了G-CSF在改善子宫内膜薄患者妊娠结局方面的潜力。结论:子宫内灌注G-CSF可改善子宫内膜血流量、免疫耐受、厚度、Treg诱导和胚胎着床,显著改善薄子宫内膜患者妊娠结局。这些发现表明,G-CSF可能是这类患者的一种有希望的治疗选择。
{"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 Q4 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

Background: 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.

Objective: 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.

Methods: 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.

Results: 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).

Conclusion: 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.

背景:γ-δ(γδ)T细胞是T细胞的一个独特亚群,其受体由γ和δ链组成。它们能直接识别应激诱导分子和癌细胞表达的非肽抗原,还能产生细胞因子并与其他免疫细胞相互作用,因此可能对基于免疫的治疗做出重要贡献:研究膀胱癌(BC)患者肿瘤引流淋巴结中Tγδ细胞的存在和频率,并评估它们与预后参数的关系:方法:将未经治疗的膀胱癌患者的49个新鲜肿瘤引流淋巴结切碎,获得单个细胞。用抗-CD3、抗-TCRγδ和抗-HLA-DR抗体对细胞进行表面染色,然后在四色FACSCalibur流式细胞仪上采集,并用FlowJo软件进行分析:BC 区域结节中平均有 2.07% ± 1.99% 的 CD3+ 淋巴细胞表现出 γδ T 表型。这些细胞中有相当大比例(37.90% ± 24.42%)表达 HLA-DR。统计分析显示,虽然γδ T 细胞的频率在不同预后的患者中没有差异,但 T4 患者的 HLA-DR+ 亚群高于 T2 患者(P=0.031)。与 II 期相比,III 期患者的这些细胞也有增加的趋势(p=0.077):这些数据共同表明,HLA-DR表达的γδT细胞与肿瘤进展相关的预后因素(较高的T组和分期)有关,这表明它们可能参与了疾病的进展。然而,未来的研究,包括更大规模队列的纵向研究,需要验证这些发现,并阐明γδ T细胞在针对BC的免疫反应中的功能作用。
{"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 Q4 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

Background: 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.

Objective: 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.

Methods: 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.

Results: 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.

Conclusion: These immunotoxin structures showed therapeutic potential against GRP78-expressing cancers, making them suitable candidates for targeted therapy pending in vivo studies.

背景:开发有效的靶向治疗方法来克服耐药性仍然是癌症研究的关键目标。免疫毒素在肿瘤检测和靶向治疗中具有双重功能。目的:通过纳米靶向结构域和外毒素效应结构域的结合,构建重组嵌合融合蛋白。该嵌合蛋白旨在结合表面表达的GRP78在癌细胞上,促进内化并诱导凋亡,从而抑制癌细胞的增殖和存活。方法:利用柔性连接体设计了两个连接VHH纳米体结构域与假单胞菌外毒素(PE)结构域II、III和Ib的构建体,并利用pET28a载体优化了这些构建体在大肠杆菌BL21 (DE3)中的表达。在表达重组蛋白后,我们纯化了重组蛋白,并在乳腺癌细胞系MDA-MB-231和MCF-7以及对照细胞系HEK-293和MDA-MB-468中测试了重组蛋白的结合能力、细胞毒性和诱导凋亡的能力。采用基于细胞的酶联免疫吸附试验(ELISA)检测其结合亲和力,Western blotting检测其内化程度,MTT检测其细胞毒性,Annexin V试剂盒检测其细胞凋亡。结果:免疫毒素特异性结合到表达csGRP78的癌细胞上。细胞毒试验结果表明,ⅰ和ⅱ两种构念的细胞毒作用与浓度和时间有关。随着这两种成分的增加,重组蛋白的作用也增加了。这两种结构都能穿透并诱导csGRP78+细胞凋亡。结论:这些免疫毒素结构对表达grp78的癌症具有治疗潜力,使其成为有待体内研究的靶向治疗的合适候选者。
{"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 Q4 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

Background: 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.

Objective: To demonstrate the enhanced antitumor efficacy of Albumin Binding Domain-conjugated IL-2 (ABD-IL-2) at a lower dose compared to IL-2.

Methods: 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.

Results: 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.

Conclusion: 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.

背景:白细胞介素-2 (IL-2)是一种众所周知的细胞因子,在刺激免疫细胞(包括自然杀伤细胞(NK)细胞和细胞毒性T细胞)中起着至关重要的作用。它已被研究作为一种免疫疗法治疗多种疾病,包括癌症。然而,由于其血清半衰期短,需要高剂量的IL-2,这可能导致全身毒性,如毛细血管渗漏综合征。目的:研究白蛋白结合域偶联白介素-2 (ABD-IL-2)在较低剂量下的抗肿瘤作用。方法:采用Ni-NTA树脂纯化IL-2和ABD-IL-2,并在其c端添加组氨酸序列进行纯化。用IL-2和ABD-IL-2刺激外周血淋巴细胞,评价其功能。将4T1细胞注射到BALB/c小鼠体内,建立乳腺癌模型并评估肺转移。结果:与阴性对照相比,两种重组蛋白均能显著刺激T淋巴细胞增殖(P=0.000, P=0.001)。在乳腺癌小鼠模型中,这两种蛋白质的使用减少了分离肿瘤的大小。对照组有更多的结节和更大的肺转移中心(P=0.000)。转移到次要淋巴器官只发生在对照组。结论:通过使用浓度为IL-2三分之一的ABD-IL-2,我们旨在降低免疫治疗中与高剂量IL-2相关的给药毒性。这种方法显示出改善基于il -2的治疗的潜力,同时最大限度地减少不良反应。
{"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 Q4 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

Background: 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.

Objective: To assess cytokine levels in breast cancer patients according to their subtypes and investigate the potential role of these cytokines in treatment.

Methods: 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.

Results: 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.

Conclusion: 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.

背景:乳腺癌是女性癌症相关死亡的主要原因。细胞因子与各种癌症有关,良性和恶性乳腺疾病都与炎症有关。然而,人们对不同亚型乳腺癌中免疫系统细胞因子反应的差异了解有限。目的:了解乳腺癌患者不同亚型细胞因子水平,探讨细胞因子在乳腺癌治疗中的潜在作用。方法:选取1-2期乳腺癌患者和健康志愿者为研究对象。根据乳腺活检结果的ER、PR、HER2受体状态和Ki67评分,将乳腺癌患者分为管腔A、管腔B和三阴性。采用多重反应法和流式细胞术定量测定所有受试者血清中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和IL-33的浓度。年龄、绝经状态和血液学参数也在组间进行比较。结果:共纳入A腔19例,B腔20例,三阴性患者18例,健康志愿者21例。乳腺癌患者的TNF-α、IL-6、IL-8、IL-10、IL-12p (p70)、IL-18和IL-23细胞因子显著高于健康志愿者。不同亚型间IFN-γ、IL-6、IL-8、IL-10、IL-12p (p70)、IL-17A、IL-18、IL-23水平差异有统计学意义,除MCP-1外,三阴性患者细胞因子水平均较低。结论:三阴性乳腺癌中细胞因子水平的降低表明免疫原性较低,由于免疫反应不足导致肿瘤进展更具侵袭性。
{"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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Iranian Journal of Immunology
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