Leptin, an immune-regulating protein, enhances the maturation of dendritic cells (DCs). We previously demonstrated that leptin and lipopolysaccharide (LPS) promote the expression of co-stimulatory molecules on the surface of DCs. Leptin/LPS-treated DCs increased T cell responses against 4T1 breast cancer in mice. Therefore, in the present study, we investigate the effects of a DC vaccine treated with leptin and LPS on the genes involved in tumor metastasis, angiogenesis, and related cytokines in a mouse model of breast cancer. Tumor induction was achieved through subcutaneous injection of 4T1 cells into syngeneic mice. On days 12 and 19, the mouse groups received the DC vaccine treated with leptin and a combination of leptin and LPS. After sacrificing the mice on day 26, the levels of IL-6 and IL-33 in the serum were assayed using the ELISA technique, and the expression levels of the VEGF, CCL2, MMP9, and CCL5 genes in the tumors were measured by Real-Time PCR. Compared to untreated tumor-bearing mice, the leptin-treated mature DC (mDC) group exhibited a significant reduction in the expression of MMP9 (0.33-fold, p = 0.01) and CCL5 (0.81-fold, p = 0.02). The leptin-LPS-treated mDC group showed decreased expression of genes involved in metastasis and tumor growth, including VEGF (0.72-fold, p = 0.03), MMP9 (0.26-fold, p = 0.001), and CCL5 (0.3-fold, p = 0.006), indicating more efficient prevention of metastasis. The CCL2 gene expression levels in both treatment groups showed a slight decreasing trend, but these changes were not statistically significant. The leptin-treated mDC group reduced IL-6 production by approximately 16% (p = 0.02), while treatment with the leptin-LPS-treated mDC significantly decreased IL-6 production by approximately 22% (p = 0.01) and increased IL-33 production by approximately 42% (p = 0.03). The findings of the present study indicate that the leptin-LPS-treated mDC vaccine group reduced the expression of genes and cytokines involved in metastasis and angiogenesis, demonstrating greater efficacy compared to the leptin-treated mDC vaccine group.
{"title":"Leptin/LPS-treated dendritic cells reduce the expression of genes involved in tumor tissue metastasis and angiogenesis in an animal model of breast cancer.","authors":"Pedram Basirjafar, Abdollah Jafarzadeh, Jafar Salimian","doi":"10.1007/s12026-024-09564-8","DOIUrl":"https://doi.org/10.1007/s12026-024-09564-8","url":null,"abstract":"<p><p>Leptin, an immune-regulating protein, enhances the maturation of dendritic cells (DCs). We previously demonstrated that leptin and lipopolysaccharide (LPS) promote the expression of co-stimulatory molecules on the surface of DCs. Leptin/LPS-treated DCs increased T cell responses against 4T1 breast cancer in mice. Therefore, in the present study, we investigate the effects of a DC vaccine treated with leptin and LPS on the genes involved in tumor metastasis, angiogenesis, and related cytokines in a mouse model of breast cancer. Tumor induction was achieved through subcutaneous injection of 4T1 cells into syngeneic mice. On days 12 and 19, the mouse groups received the DC vaccine treated with leptin and a combination of leptin and LPS. After sacrificing the mice on day 26, the levels of IL-6 and IL-33 in the serum were assayed using the ELISA technique, and the expression levels of the VEGF, CCL2, MMP9, and CCL5 genes in the tumors were measured by Real-Time PCR. Compared to untreated tumor-bearing mice, the leptin-treated mature DC (mDC) group exhibited a significant reduction in the expression of MMP9 (0.33-fold, p = 0.01) and CCL5 (0.81-fold, p = 0.02). The leptin-LPS-treated mDC group showed decreased expression of genes involved in metastasis and tumor growth, including VEGF (0.72-fold, p = 0.03), MMP9 (0.26-fold, p = 0.001), and CCL5 (0.3-fold, p = 0.006), indicating more efficient prevention of metastasis. The CCL2 gene expression levels in both treatment groups showed a slight decreasing trend, but these changes were not statistically significant. The leptin-treated mDC group reduced IL-6 production by approximately 16% (p = 0.02), while treatment with the leptin-LPS-treated mDC significantly decreased IL-6 production by approximately 22% (p = 0.01) and increased IL-33 production by approximately 42% (p = 0.03). The findings of the present study indicate that the leptin-LPS-treated mDC vaccine group reduced the expression of genes and cytokines involved in metastasis and angiogenesis, demonstrating greater efficacy compared to the leptin-treated mDC vaccine group.</p>","PeriodicalId":13389,"journal":{"name":"Immunologic Research","volume":"73 1","pages":"2"},"PeriodicalIF":3.3,"publicationDate":"2024-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142806925","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}
Pub Date : 2024-12-10DOI: 10.1007/s12026-024-09578-2
Hai-Yan Zhu, Hai-Juan Wang, Peng Liu
Neutrophil proteinase 3 (PR3), cathepsin G, elastase, and neutrophil serine protease 4 constitute the neutrophil serine protease family. These four members share varying sequence homology and functional similarities with each other. However, PR3 stands out as a unique autoantigen, serving as a primary autoantigen in anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis. Numerous studies have documented or reviewed the molecular pathogenesis or diagnostic utility of PR3 in ANCA-associated vasculitis. Nevertheless, the role of PR3 in other areas, particularly within the hematopoietic system, appears to have been overlooked. Indeed, beyond its involvement in vasculitis, PR3 contributes to cell apoptosis, hematopoietic abnormalities, diabetic ketoacidosis, and various other inflammatory diseases. In this study, we aim to summarize the research on the function of neutrophil PR3 in hematopoiesis and to elucidate its potential role in neutrophil aging and inflammatory diseases.
{"title":"Versatile roles for neutrophil proteinase 3 in hematopoiesis and inflammation.","authors":"Hai-Yan Zhu, Hai-Juan Wang, Peng Liu","doi":"10.1007/s12026-024-09578-2","DOIUrl":"10.1007/s12026-024-09578-2","url":null,"abstract":"<p><p>Neutrophil proteinase 3 (PR3), cathepsin G, elastase, and neutrophil serine protease 4 constitute the neutrophil serine protease family. These four members share varying sequence homology and functional similarities with each other. However, PR3 stands out as a unique autoantigen, serving as a primary autoantigen in anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis. Numerous studies have documented or reviewed the molecular pathogenesis or diagnostic utility of PR3 in ANCA-associated vasculitis. Nevertheless, the role of PR3 in other areas, particularly within the hematopoietic system, appears to have been overlooked. Indeed, beyond its involvement in vasculitis, PR3 contributes to cell apoptosis, hematopoietic abnormalities, diabetic ketoacidosis, and various other inflammatory diseases. In this study, we aim to summarize the research on the function of neutrophil PR3 in hematopoiesis and to elucidate its potential role in neutrophil aging and inflammatory diseases.</p>","PeriodicalId":13389,"journal":{"name":"Immunologic Research","volume":"73 1","pages":"1"},"PeriodicalIF":3.3,"publicationDate":"2024-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142806973","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}
Pub Date : 2024-12-01Epub Date: 2024-10-02DOI: 10.1007/s12026-024-09543-z
Fulvia Ceccarelli, Francesco Natalucci, Claudia Ciancarella, Licia Picciariello, Valeria Moretti, Francesca Romana Spinelli, Cristiano Alessandri, Fabrizio Conti
We analysed the change in the positioning of belimumab (BLM) in systemic lupus erythematosus (SLE) treatment in the first decade of real-life use, by providing data about patients treated by this biological drug in the Sapienza Lupus Cohort. We evaluated SLE patients treated by BLM according to the current clinical practice. Data of each patient were collected, focusing on previous and concomitant treatments. Finally, the drug retention rate was assessed. Since August 2013, 138 SLE patients started BLM (M/F 7/131; median age 49 years, IQR 13.25; median disease duration 214 months, IQR 180). To evaluate the change in BLM positioning, we divided patients according to the date of starting treatment as below: patients treated from 2013 to 2018 (period 1) and those treated since 2019 to date (period 2). Indeed, the median number of previous immunosuppressant drugs was significantly higher in patients treated in period 1 [3 (IQR 1.25) versus 1 (IQR 1.75), p = 0.0002]. Furthermore, 15.9% of patients treated in period 2 were not previously treated by immunosuppressant drugs, compared with 5.2% in period 1 (p = 0.01). Finally, the 24-month drug survival was significantly higher in patients previously treated with ≤ 1 immunosuppressant drug in comparison with those treated with ≥ 2 drugs (69.1% versus 43.4%, p = 0.0097, HR 0.49; 95% CI 0.27-0.88). Our data clearly described the progressive anticipation of BLM prescription in the first 10 years of clinical practice, underlining as choosing earlier biological agents could positively influence the drug retention rate.
{"title":"Belimumab 10 years later: how drug positioning has changed.","authors":"Fulvia Ceccarelli, Francesco Natalucci, Claudia Ciancarella, Licia Picciariello, Valeria Moretti, Francesca Romana Spinelli, Cristiano Alessandri, Fabrizio Conti","doi":"10.1007/s12026-024-09543-z","DOIUrl":"10.1007/s12026-024-09543-z","url":null,"abstract":"<p><p>We analysed the change in the positioning of belimumab (BLM) in systemic lupus erythematosus (SLE) treatment in the first decade of real-life use, by providing data about patients treated by this biological drug in the Sapienza Lupus Cohort. We evaluated SLE patients treated by BLM according to the current clinical practice. Data of each patient were collected, focusing on previous and concomitant treatments. Finally, the drug retention rate was assessed. Since August 2013, 138 SLE patients started BLM (M/F 7/131; median age 49 years, IQR 13.25; median disease duration 214 months, IQR 180). To evaluate the change in BLM positioning, we divided patients according to the date of starting treatment as below: patients treated from 2013 to 2018 (period 1) and those treated since 2019 to date (period 2). Indeed, the median number of previous immunosuppressant drugs was significantly higher in patients treated in period 1 [3 (IQR 1.25) versus 1 (IQR 1.75), p = 0.0002]. Furthermore, 15.9% of patients treated in period 2 were not previously treated by immunosuppressant drugs, compared with 5.2% in period 1 (p = 0.01). Finally, the 24-month drug survival was significantly higher in patients previously treated with ≤ 1 immunosuppressant drug in comparison with those treated with ≥ 2 drugs (69.1% versus 43.4%, p = 0.0097, HR 0.49; 95% CI 0.27-0.88). Our data clearly described the progressive anticipation of BLM prescription in the first 10 years of clinical practice, underlining as choosing earlier biological agents could positively influence the drug retention rate.</p>","PeriodicalId":13389,"journal":{"name":"Immunologic Research","volume":" ","pages":"1441-1446"},"PeriodicalIF":3.3,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11618203/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142361361","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-12-01Epub Date: 2024-08-20DOI: 10.1007/s12026-024-09531-3
Wei Chen, Yao Xie, Fan Li, Pengfei Wen, Lin Wang
EBV-associated T/NK-cell lymphoproliferative diseases (EBV-T/NK-LPDs) are characterized by the clonal proliferation of EBV-positive ( +) T/NK cells. EBV is typically latent in B cells and the mechanism by which the EBV genome invades T/NK cells remains unknown. Recent studies have demonstrated that exosomes derived from EBV + B cells play a pivotal role in immunosuppressive microenvironment remodeling. Moreover, the existence of an immunosuppressive microenvironment is known to be critical in the development of EBV-T/NK-LPDs. Hence, we hypothesized that exosomes derived from EBV + B cells might promote the development of EBV-T/NK-LPDs by stimulating immune evasion. In this study, we utilized paraffin sections to clarify the STAT3/IL-10/PD-L1-associated immunosuppressive microenvironment in EBV-T/NK-LPDs. Further, we extracted exosomes from BL2009 (EBV + B cell lymphoma) and CA46 (EBV- B cell lymphoma) cell lines to co-culture with cutaneous T-cell lymphoma (CTCL) cell lines, to verify the changes in the above immune evasion pathway. The paraffin sections of EBV-T/NK-LPDs showed high-expression levels of IL-10/PD-L1, which might be related to the phosphorylation of STAT3. Exosomes derived from EBV + B cells could significantly activate the STAT3/IL-10/PD-L1 pathway. After being treated with C188-9, EBV + B cell-derived exosomes were no longer able to stimulate the expression of IL-10/PD-L1 in CTCL cells. EBV-T/NK-LPDs have a STAT3/IL-10/PD-L1 overactivation-associated immunosuppressive microenvironment. Our study elucidated part of this mechanism. Exosomes derived from EBV + B could induce phosphorylation of STAT3 in CTCL cells, leading to the overexpression of IL-10/PD-L1. Our findings might shed light on new directions for understanding immune evasion in EBV-T/NK-LPDs.
EBV相关T/NK细胞淋巴增殖性疾病(EBV-T/NK-LPDs)的特征是EBV阳性(+)T/NK细胞的克隆性增殖。EBV 通常潜伏在 B 细胞中,EBV 基因组入侵 T/NK 细胞的机制仍不清楚。最近的研究表明,来自 EBV + B 细胞的外泌体在免疫抑制微环境重塑中起着关键作用。此外,众所周知,免疫抑制微环境的存在对 EBV-T/NK-LPDs 的发展至关重要。因此,我们假设来自 EBV + B 细胞的外泌体可能会通过刺激免疫逃避来促进 EBV-T/NK-LPDs 的发展。在本研究中,我们利用石蜡切片明确了EBV-T/NK-LPDs中与STAT3/IL-10/PD-L1相关的免疫抑制微环境。此外,我们还从 BL2009(EBV + B 细胞淋巴瘤)和 CA46(EBV- B 细胞淋巴瘤)细胞系中提取外泌体,与皮肤 T 细胞淋巴瘤(CTCL)细胞系共培养,以验证上述免疫逃避途径的变化。EBV-T/NK-LPD的石蜡切片显示IL-10/PD-L1的高表达水平,这可能与STAT3的磷酸化有关。提取自EBV + B细胞的外泌体可显著激活STAT3/IL-10/PD-L1通路。经C188-9处理后,EBV + B细胞衍生的外泌体不再能刺激CTCL细胞中IL-10/PD-L1的表达。EBV-T/NK-LPDs具有STAT3/IL-10/PD-L1过度激活相关的免疫抑制微环境。我们的研究阐明了这一机制的一部分。来自 EBV + B 的外泌体可诱导 CTCL 细胞中的 STAT3 磷酸化,从而导致 IL-10/PD-L1 的过度表达。我们的发现可能为了解EBV-T/NK-LPD的免疫逃避提供了新的方向。
{"title":"EBV + B cell-derived exosomes promote EBV-associated T/NK-cell lymphoproliferative disease immune evasion by STAT3/IL-10/PD-L1 pathway.","authors":"Wei Chen, Yao Xie, Fan Li, Pengfei Wen, Lin Wang","doi":"10.1007/s12026-024-09531-3","DOIUrl":"10.1007/s12026-024-09531-3","url":null,"abstract":"<p><p>EBV-associated T/NK-cell lymphoproliferative diseases (EBV-T/NK-LPDs) are characterized by the clonal proliferation of EBV-positive ( +) T/NK cells. EBV is typically latent in B cells and the mechanism by which the EBV genome invades T/NK cells remains unknown. Recent studies have demonstrated that exosomes derived from EBV + B cells play a pivotal role in immunosuppressive microenvironment remodeling. Moreover, the existence of an immunosuppressive microenvironment is known to be critical in the development of EBV-T/NK-LPDs. Hence, we hypothesized that exosomes derived from EBV + B cells might promote the development of EBV-T/NK-LPDs by stimulating immune evasion. In this study, we utilized paraffin sections to clarify the STAT3/IL-10/PD-L1-associated immunosuppressive microenvironment in EBV-T/NK-LPDs. Further, we extracted exosomes from BL2009 (EBV + B cell lymphoma) and CA46 (EBV- B cell lymphoma) cell lines to co-culture with cutaneous T-cell lymphoma (CTCL) cell lines, to verify the changes in the above immune evasion pathway. The paraffin sections of EBV-T/NK-LPDs showed high-expression levels of IL-10/PD-L1, which might be related to the phosphorylation of STAT3. Exosomes derived from EBV + B cells could significantly activate the STAT3/IL-10/PD-L1 pathway. After being treated with C188-9, EBV + B cell-derived exosomes were no longer able to stimulate the expression of IL-10/PD-L1 in CTCL cells. EBV-T/NK-LPDs have a STAT3/IL-10/PD-L1 overactivation-associated immunosuppressive microenvironment. Our study elucidated part of this mechanism. Exosomes derived from EBV + B could induce phosphorylation of STAT3 in CTCL cells, leading to the overexpression of IL-10/PD-L1. Our findings might shed light on new directions for understanding immune evasion in EBV-T/NK-LPDs.</p>","PeriodicalId":13389,"journal":{"name":"Immunologic Research","volume":" ","pages":"1327-1336"},"PeriodicalIF":3.3,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11618311/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142008757","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-12-01Epub Date: 2024-11-04DOI: 10.1007/s12026-024-09549-7
Fei Ma, Xiaoyang Feng, Shiyu Feng, Jin Liu, Jia Li, Lihua Mo, Lingzhi Xu, Yulei Liu, Jiaman Wu, Pingchang Yang, Yan Ning
The pathogenesis of recurrent pregnancy loss (RPL) is unclear. RPL may have an association with disruption of immune tolerance. The aim of this study is to characterize the inducibility of immune regulatory ability in peripheral naïve B cells of patients with RPL. In this study, blood samples were taken from patients with RPL. B220+ B cells were isolated by flow cytometry cell sorting. The gene profile of B cells was analyzed using RNA sequencing (RNAseq). The results showed that peripheral B220+ B cells of RPL patients had lower expression of IL10 and exacerbated ER stress. The induction of IL10 expression in peripheral B220+ B cells of RPL patients were impaired. High ubiquitination of c-Maf inducing protein (CMIP) was detected in RPL B cells. Exposure to thapsigargin (an ER stress agonist) decreased the amount of CMIP in B cells. The effects of ER stress on reducing CMIP quantity in B cells were mediated by the histone H2B E3 ubiquitin ligase ring finger protein 20 (RNF20). Inhibition of RNF20 or ER stress restored the inducibility of immune regulatory functions of B220+ B cells of RPL patients. In summary, peripheral B cells in patients with RPL show impaired immune regulation capacity, in which exacerbated ER stress plays a crucial role. Regulation of ER stress or inhibition of RNF20 can restore the immune regulatory capacity in the B cells.
复发性妊娠失败(RPL)的发病机制尚不清楚。RPL可能与免疫耐受的破坏有关。本研究的目的是鉴定 RPL 患者外周幼稚 B 细胞免疫调节能力的诱导性。本研究采集了 RPL 患者的血液样本。通过流式细胞术细胞分拣分离出 B220+ B 细胞。利用 RNA 测序(RNAseq)分析了 B 细胞的基因图谱。结果显示,RPL 患者外周 B220+ B 细胞的 IL10 表达较低,ER 应激加剧。RPL患者外周B220+ B细胞中IL10的诱导表达受损。在RPL B细胞中检测到了c-Maf诱导蛋白(CMIP)的高泛素化。暴露于硫司加精(一种ER应激激动剂)可减少B细胞中CMIP的数量。ER应激对减少B细胞中CMIP数量的影响是由组蛋白H2B E3泛素连接酶环指蛋白20(RNF20)介导的。抑制 RNF20 或 ER 应激可恢复 RPL 患者 B220+ B 细胞免疫调节功能的诱导性。总之,RPL 患者的外周 B 细胞显示出免疫调节能力受损,ER 应激的加剧在其中发挥了关键作用。调节ER应激或抑制RNF20可恢复B细胞的免疫调节能力。
{"title":"Impaired inducibility of immune regulatory capacity of peripheral B cells of patients with recurrent pregnancy loss.","authors":"Fei Ma, Xiaoyang Feng, Shiyu Feng, Jin Liu, Jia Li, Lihua Mo, Lingzhi Xu, Yulei Liu, Jiaman Wu, Pingchang Yang, Yan Ning","doi":"10.1007/s12026-024-09549-7","DOIUrl":"10.1007/s12026-024-09549-7","url":null,"abstract":"<p><p>The pathogenesis of recurrent pregnancy loss (RPL) is unclear. RPL may have an association with disruption of immune tolerance. The aim of this study is to characterize the inducibility of immune regulatory ability in peripheral naïve B cells of patients with RPL. In this study, blood samples were taken from patients with RPL. B220<sup>+</sup> B cells were isolated by flow cytometry cell sorting. The gene profile of B cells was analyzed using RNA sequencing (RNAseq). The results showed that peripheral B220<sup>+</sup> B cells of RPL patients had lower expression of IL10 and exacerbated ER stress. The induction of IL10 expression in peripheral B220<sup>+</sup> B cells of RPL patients were impaired. High ubiquitination of c-Maf inducing protein (CMIP) was detected in RPL B cells. Exposure to thapsigargin (an ER stress agonist) decreased the amount of CMIP in B cells. The effects of ER stress on reducing CMIP quantity in B cells were mediated by the histone H2B E3 ubiquitin ligase ring finger protein 20 (RNF20). Inhibition of RNF20 or ER stress restored the inducibility of immune regulatory functions of B220<sup>+</sup> B cells of RPL patients. In summary, peripheral B cells in patients with RPL show impaired immune regulation capacity, in which exacerbated ER stress plays a crucial role. Regulation of ER stress or inhibition of RNF20 can restore the immune regulatory capacity in the B cells.</p>","PeriodicalId":13389,"journal":{"name":"Immunologic Research","volume":" ","pages":"1502-1514"},"PeriodicalIF":3.3,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142568196","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}
Pub Date : 2024-12-01Epub Date: 2024-09-05DOI: 10.1007/s12026-024-09536-y
Awais Ali, Abdulaziz Alamri, Azraida Hajar
The complex relationship between natural killer (NK) cells and dendritic cells (DCs) within the tumor microenvironment significantly impacts the success of cancer immunotherapy. Recent advancements in cancer treatment have sought to bolster innate and adaptive immune responses through diverse modalities, aiming to tilt the immune equilibrium toward tumor elimination. Optimal antitumor immunity entails a multifaceted interplay involving NK cells, T cells and DCs, orchestrating immune effector functions. Although DC-based vaccines and NK cells' cytotoxic capabilities hold substantial therapeutic potential, their interaction is frequently hindered by immunosuppressive elements such as myeloid-derived suppressor cells (MDSCs) and regulatory T cells. Chemokines and cytokines, such as CXCL12, CCL2, interferons, and interleukins, play crucial roles in modulating NK/DC interactions and enhancing immune responses. This review elucidates the mechanisms underlying NK/DC interaction, emphasizing their pivotal roles in augmenting antitumor immune responses and the impediments posed by tumor-induced immunosuppression. Furthermore, it explores the therapeutic prospects of restoring NK/DC crosstalk, highlighting the significance of molecules like Sema3E/PlexinD1 in this context, offering potential avenues for enhancing the effectiveness of current immunotherapeutic strategies and advancing cancer treatment paradigms. Harnessing the dynamic interplay between NK and DC cells, including the modulation of Sema3E/PlexinD1 signaling, holds promise for developing more potent therapies that harness the immune system's full potential in combating cancer.
肿瘤微环境中自然杀伤细胞(NK)和树突状细胞(DCs)之间的复杂关系对癌症免疫疗法的成功与否有着重大影响。癌症治疗的最新进展是通过多种方式增强先天性和适应性免疫反应,目的是使免疫平衡向消除肿瘤的方向倾斜。最佳的抗肿瘤免疫需要 NK 细胞、T 细胞和 DC 的多方面相互作用,协调免疫效应功能。虽然基于 DC 的疫苗和 NK 细胞的细胞毒性能力具有巨大的治疗潜力,但它们之间的相互作用经常受到免疫抑制因素的阻碍,如髓源性抑制细胞(MDSCs)和调节性 T 细胞。CXCL12、CCL2、干扰素和白细胞介素等趋化因子和细胞因子在调节 NK/DC 相互作用和增强免疫反应方面起着至关重要的作用。本综述阐明了 NK/DC 相互作用的基本机制,强调了它们在增强抗肿瘤免疫反应中的关键作用以及肿瘤诱导的免疫抑制所造成的障碍。此外,它还探讨了恢复 NK/DC 相互交织的治疗前景,强调了 Sema3E/PlexinD1 等分子在这方面的重要性,为提高当前免疫治疗策略的有效性和推进癌症治疗范例提供了潜在的途径。利用 NK 细胞和 DC 细胞之间的动态相互作用,包括对 Sema3E/PlexinD1 信号的调节,有望开发出更有效的疗法,充分发挥免疫系统在抗击癌症方面的潜力。
{"title":"NK/DC crosstalk-modulating antitumor activity via Sema3E/PlexinD1 axis for enhanced cancer immunotherapy.","authors":"Awais Ali, Abdulaziz Alamri, Azraida Hajar","doi":"10.1007/s12026-024-09536-y","DOIUrl":"10.1007/s12026-024-09536-y","url":null,"abstract":"<p><p>The complex relationship between natural killer (NK) cells and dendritic cells (DCs) within the tumor microenvironment significantly impacts the success of cancer immunotherapy. Recent advancements in cancer treatment have sought to bolster innate and adaptive immune responses through diverse modalities, aiming to tilt the immune equilibrium toward tumor elimination. Optimal antitumor immunity entails a multifaceted interplay involving NK cells, T cells and DCs, orchestrating immune effector functions. Although DC-based vaccines and NK cells' cytotoxic capabilities hold substantial therapeutic potential, their interaction is frequently hindered by immunosuppressive elements such as myeloid-derived suppressor cells (MDSCs) and regulatory T cells. Chemokines and cytokines, such as CXCL12, CCL2, interferons, and interleukins, play crucial roles in modulating NK/DC interactions and enhancing immune responses. This review elucidates the mechanisms underlying NK/DC interaction, emphasizing their pivotal roles in augmenting antitumor immune responses and the impediments posed by tumor-induced immunosuppression. Furthermore, it explores the therapeutic prospects of restoring NK/DC crosstalk, highlighting the significance of molecules like Sema3E/PlexinD1 in this context, offering potential avenues for enhancing the effectiveness of current immunotherapeutic strategies and advancing cancer treatment paradigms. Harnessing the dynamic interplay between NK and DC cells, including the modulation of Sema3E/PlexinD1 signaling, holds promise for developing more potent therapies that harness the immune system's full potential in combating cancer.</p>","PeriodicalId":13389,"journal":{"name":"Immunologic Research","volume":" ","pages":"1217-1228"},"PeriodicalIF":3.3,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142132615","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}
Pub Date : 2024-12-01Epub Date: 2024-08-24DOI: 10.1007/s12026-024-09528-y
Yucai Ye, Juan Wang, Bahu Bao, Guorong Chen, Aoyan Hu, Jingzi Sun, Weiying Liu
Good syndrome (GS), a rare acquired immunodeficiency disorder characterized by thymoma and hypogammaglobulinemia, predisposes individuals to recurrent infections. This study reports a case of a 37-year-old male GS with multiple pulmonary infections and reviews relevant literature. The patient, with a history of thymoma resection, experienced multiple hospitalizations due to lung infections and neutropenia. The alveolar lavage fluid was detected by macro-genomic sequencing (NGS) to detect multiple pathogens, and targeted anti-infective and immunity-enhancing treatments led to improved symptoms and normal neutrophil counts. A literature review of 98 case reports from 2000 to 2023 was conducted, summarizing the associated diseases and pathogens in GS patients. Regular immunoglobulin monitoring in thymoma patients is essential for early GS diagnosis. When empirical antimicrobial therapy fails, mNGS for pathogen detection and targeted therapy are crucial, and regular IVIG injections can reduce infection rates in GS patients.
{"title":"Good syndrome combined with multiple microbial pulmonary infections: case report and review of the literature.","authors":"Yucai Ye, Juan Wang, Bahu Bao, Guorong Chen, Aoyan Hu, Jingzi Sun, Weiying Liu","doi":"10.1007/s12026-024-09528-y","DOIUrl":"10.1007/s12026-024-09528-y","url":null,"abstract":"<p><p>Good syndrome (GS), a rare acquired immunodeficiency disorder characterized by thymoma and hypogammaglobulinemia, predisposes individuals to recurrent infections. This study reports a case of a 37-year-old male GS with multiple pulmonary infections and reviews relevant literature. The patient, with a history of thymoma resection, experienced multiple hospitalizations due to lung infections and neutropenia. The alveolar lavage fluid was detected by macro-genomic sequencing (NGS) to detect multiple pathogens, and targeted anti-infective and immunity-enhancing treatments led to improved symptoms and normal neutrophil counts. A literature review of 98 case reports from 2000 to 2023 was conducted, summarizing the associated diseases and pathogens in GS patients. Regular immunoglobulin monitoring in thymoma patients is essential for early GS diagnosis. When empirical antimicrobial therapy fails, mNGS for pathogen detection and targeted therapy are crucial, and regular IVIG injections can reduce infection rates in GS patients.</p>","PeriodicalId":13389,"journal":{"name":"Immunologic Research","volume":" ","pages":"1288-1298"},"PeriodicalIF":3.3,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142046625","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}
Hereditary angioedema (HAE) is a rare genetic disorder. The pattern of HAE is different in children as compared to adults. There is limited literature from developing countries where all first-line treatments are either unavailable or not easily accessible. Data of children with HAE were retrieved from medical records of patients registered in the Pediatric Immunodeficiency Clinic at our institute. Of the 206 patients with HAE, 61 were diagnosed before the age of 18 years. Male: female ratio was 1.1:1. Median age at onset of symptoms and diagnosis were 6.2 years (range 1-17 years) and 10.7 years (range 1.5-18 years) respectively. Median delay in diagnosis was 4.9 years (range 0-16 years). The commonest presentation was facial swelling (51/61) followed by swelling of extremities (47/61). Laryngeal edema and abdominal symptoms were reported in 28/61 and 31/61 patients respectively. Abdominal attacks were found to be less common in children as compared to adults. Most patients in our cohort received fresh-frozen plasma (n = 5/61) as on-demand therapy. Long-term prophylaxis included attenuated androgens (n = 25/61) and tranexamic acid (n = 23/61). Median duration of follow-up was 2242 patient months. One patient died on follow-up in this cohort. This is the largest single-centre cohort of pediatric HAE from resource-constrained settings. Facial attacks were more common, and there were significant delays in diagnosis when the age of onset of symptoms was younger. Gastrointestinal symptoms were less common in children than adults. HIGHLIGHTS: One of the largest single-centre cohorts of pediatric HAE and the only one from resource-constrained settings. There were significant delays in diagnosis when the age of onset of symptoms was younger. Abdominal attacks were found to be less common in children as compared to adults.
{"title":"Clinical profile and management of pediatric hereditary angioedema in resource-constrained settings: our experience from a single centre in North India.","authors":"Ankur Kumar Jindal, Prabal Barman, Suprit Basu, Reva Tyagi, Archan Sil, Sanchi Chawla, Sanghamitra Machhua, Gurjit Kaur, Saniya Sharma, Manpreet Dhaliwal, Anuradha Bishnoi, Keshavmurthy Vinay, Pandiarajan Vignesh, Rakesh Kumar Pilania, Deepti Suri, Ravinder Garg, Amit Rawat, Sendhil M Kumaran, Sunil Dogra, Henriette Farkas, Hilary Longhurst, Surjit Singh","doi":"10.1007/s12026-024-09547-9","DOIUrl":"10.1007/s12026-024-09547-9","url":null,"abstract":"<p><p>Hereditary angioedema (HAE) is a rare genetic disorder. The pattern of HAE is different in children as compared to adults. There is limited literature from developing countries where all first-line treatments are either unavailable or not easily accessible. Data of children with HAE were retrieved from medical records of patients registered in the Pediatric Immunodeficiency Clinic at our institute. Of the 206 patients with HAE, 61 were diagnosed before the age of 18 years. Male: female ratio was 1.1:1. Median age at onset of symptoms and diagnosis were 6.2 years (range 1-17 years) and 10.7 years (range 1.5-18 years) respectively. Median delay in diagnosis was 4.9 years (range 0-16 years). The commonest presentation was facial swelling (51/61) followed by swelling of extremities (47/61). Laryngeal edema and abdominal symptoms were reported in 28/61 and 31/61 patients respectively. Abdominal attacks were found to be less common in children as compared to adults. Most patients in our cohort received fresh-frozen plasma (n = 5/61) as on-demand therapy. Long-term prophylaxis included attenuated androgens (n = 25/61) and tranexamic acid (n = 23/61). Median duration of follow-up was 2242 patient months. One patient died on follow-up in this cohort. This is the largest single-centre cohort of pediatric HAE from resource-constrained settings. Facial attacks were more common, and there were significant delays in diagnosis when the age of onset of symptoms was younger. Gastrointestinal symptoms were less common in children than adults. HIGHLIGHTS: One of the largest single-centre cohorts of pediatric HAE and the only one from resource-constrained settings. There were significant delays in diagnosis when the age of onset of symptoms was younger. Abdominal attacks were found to be less common in children as compared to adults.</p>","PeriodicalId":13389,"journal":{"name":"Immunologic Research","volume":" ","pages":"1479-1488"},"PeriodicalIF":3.3,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142345937","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}
Pub Date : 2024-12-01Epub Date: 2024-09-25DOI: 10.1007/s12026-024-09544-y
Chunhong Li, Yuhua Mao, Jiahua Hu, Chunchun Su, Mengqin Li, Haiyin Tan
Lung adenocarcinoma (LUAD) is a malignancy affecting the respiratory system. Most patients are diagnosed with advanced or metastatic lung cancer due to the fact that most of their clinical symptoms are insidious, resulting in a bleak prognosis. Given that abnormal reprogramming of asparagine metabolism (AM) has emerged as an emerging therapeutic target for anti-tumor therapy. However, the clinical significance of abnormal reprogramming of AM in LUAD patients is unclear. In this study, we collected 864 asparagine metabolism-related genes (AMGs) and used a machine-learning computational framework to develop an asparagine metabolism immunity index (AMII) for LUAD patients. Through the utilization of median AMII scores, LUAD patients were segregated into either a low-AMII group or a high-AMII group. We observed outstanding performance of AMII in predicting survival prognosis in LUAD patients in the TCGA-LUAD cohort and in three externally independently validated GEO cohorts (GSE72094, GSE37745, and GSE30219), and poorer prognosis for LUAD patients in the high-AMII group. The results of univariate and multivariate analyses showed that AMII can be used as an independent risk factor for LUAD patients. In addition, the results of C-index analysis and decision analysis showed that AMII-based nomograms had a robust performance in terms of accuracy of prognostic prediction and net clinical benefit in patients with LUAD. Excitingly, LUAD patients in the low-AMII group were more sensitive to commonly used chemotherapeutic drugs. Consequently, AMII is expected to be a novel diagnostic tool for clinical classification, providing valuable insights for clinical decision-making and personalized management of LUAD patients.
{"title":"Integrating machine learning and multi-omics analysis to develop an asparagine metabolism immunity index for improving clinical outcome and drug sensitivity in lung adenocarcinoma.","authors":"Chunhong Li, Yuhua Mao, Jiahua Hu, Chunchun Su, Mengqin Li, Haiyin Tan","doi":"10.1007/s12026-024-09544-y","DOIUrl":"10.1007/s12026-024-09544-y","url":null,"abstract":"<p><p>Lung adenocarcinoma (LUAD) is a malignancy affecting the respiratory system. Most patients are diagnosed with advanced or metastatic lung cancer due to the fact that most of their clinical symptoms are insidious, resulting in a bleak prognosis. Given that abnormal reprogramming of asparagine metabolism (AM) has emerged as an emerging therapeutic target for anti-tumor therapy. However, the clinical significance of abnormal reprogramming of AM in LUAD patients is unclear. In this study, we collected 864 asparagine metabolism-related genes (AMGs) and used a machine-learning computational framework to develop an asparagine metabolism immunity index (AMII) for LUAD patients. Through the utilization of median AMII scores, LUAD patients were segregated into either a low-AMII group or a high-AMII group. We observed outstanding performance of AMII in predicting survival prognosis in LUAD patients in the TCGA-LUAD cohort and in three externally independently validated GEO cohorts (GSE72094, GSE37745, and GSE30219), and poorer prognosis for LUAD patients in the high-AMII group. The results of univariate and multivariate analyses showed that AMII can be used as an independent risk factor for LUAD patients. In addition, the results of C-index analysis and decision analysis showed that AMII-based nomograms had a robust performance in terms of accuracy of prognostic prediction and net clinical benefit in patients with LUAD. Excitingly, LUAD patients in the low-AMII group were more sensitive to commonly used chemotherapeutic drugs. Consequently, AMII is expected to be a novel diagnostic tool for clinical classification, providing valuable insights for clinical decision-making and personalized management of LUAD patients.</p>","PeriodicalId":13389,"journal":{"name":"Immunologic Research","volume":" ","pages":"1447-1469"},"PeriodicalIF":3.3,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142345938","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}
Pub Date : 2024-12-01Epub Date: 2024-10-16DOI: 10.1007/s12026-024-09539-9
Bicheng Xie, Anxing Zhang, Canmei Li, Yu Liu, Yao Deng, Ruochang Li, Haichun Qin, Bian Wu, Tian He, Danfeng Lan
Sorting nexin 10 (SNX10) expression induces intestinal barrier dysfunction and inflammatory responses; in contrast, its inhibition promotes intestinal mucosal healing through sterol regulatory element-binding protein 2 (SREBP2)-mediated cholesterol synthesis. However, its regulatory mechanism for the pathogenesis of inflammatory bowel disease (IBD) remains unclear. In this study, we examined SNX10 and SREBP2 expression in ulcerative colitis (UC) and Crohn's disease (CD). A total of 30 and 28 patients with UC and CD, respectively, were recruited. The expression of SNX10 and SREBP2 in the colonic mucosa was measured by immunohistochemistry (IHC). We discovered that patients with CD had significantly higher expression levels of SNX10 and SREBP2 than patients with UC and healthy controls. In addition, the expression of SREBP2 in patients with UC was significantly higher than that in healthy controls. In our study, we indicated that SNX10 and SREBP2 may serve as biomarkers for identifying patients with UC and CD, thereby providing a clinical therapeutic strategy for the treatment of IBD by inhibiting SNX10.
{"title":"Differential analysis of sorting nexin 10 and sterol regulatory element-binding protein 2 expression in inflammatory bowel disease.","authors":"Bicheng Xie, Anxing Zhang, Canmei Li, Yu Liu, Yao Deng, Ruochang Li, Haichun Qin, Bian Wu, Tian He, Danfeng Lan","doi":"10.1007/s12026-024-09539-9","DOIUrl":"10.1007/s12026-024-09539-9","url":null,"abstract":"<p><p>Sorting nexin 10 (SNX10) expression induces intestinal barrier dysfunction and inflammatory responses; in contrast, its inhibition promotes intestinal mucosal healing through sterol regulatory element-binding protein 2 (SREBP2)-mediated cholesterol synthesis. However, its regulatory mechanism for the pathogenesis of inflammatory bowel disease (IBD) remains unclear. In this study, we examined SNX10 and SREBP2 expression in ulcerative colitis (UC) and Crohn's disease (CD). A total of 30 and 28 patients with UC and CD, respectively, were recruited. The expression of SNX10 and SREBP2 in the colonic mucosa was measured by immunohistochemistry (IHC). We discovered that patients with CD had significantly higher expression levels of SNX10 and SREBP2 than patients with UC and healthy controls. In addition, the expression of SREBP2 in patients with UC was significantly higher than that in healthy controls. In our study, we indicated that SNX10 and SREBP2 may serve as biomarkers for identifying patients with UC and CD, thereby providing a clinical therapeutic strategy for the treatment of IBD by inhibiting SNX10.</p>","PeriodicalId":13389,"journal":{"name":"Immunologic Research","volume":" ","pages":"1417-1423"},"PeriodicalIF":3.3,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142464244","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}