Frontiers in Immunology最新文献

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Immunomodulation of human T cells by microbubble-mediated focused ultrasound. 微泡介导的聚焦超声对人类 T 细胞的免疫调节作用
IF 5.7 2区 医学
Frontiers in Immunology Pub Date : 2024-10-22 eCollection Date: 2024-01-01 DOI: 10.3389/fimmu.2024.1486744
Ana Baez, Davindra Singh, Stephanie He, Mehri Hajiaghayi, Fatemeh Gholizadeh, Peter J Darlington, Brandon Helfield
{"title":"Immunomodulation of human T cells by microbubble-mediated focused ultrasound.","authors":"Ana Baez, Davindra Singh, Stephanie He, Mehri Hajiaghayi, Fatemeh Gholizadeh, Peter J Darlington, Brandon Helfield","doi":"10.3389/fimmu.2024.1486744","DOIUrl":"10.3389/fimmu.2024.1486744","url":null,"abstract":"<p><p>While met with initial and ground-breaking success targeting blood borne cancers, cellular immunotherapy remains significantly hindered in the context of solid tumors by the tumor microenvironment. Focused ultrasound, in conjunction with microbubbles, has found tremendous potential as a targeted and local drug/gene delivery technique for cancer therapy. The specific immunomodulating effects of this technique on immune cells, including T-cells, remain unexplored. Here, with freshly isolated human immune cells, we examine how focused ultrasound can viably modulate immune cell membrane permeability and influence the secretion of over 90 cytokines, chemokines and other analytes relevant to a potent immune response against cancer. We determine that microbubble-mediated focused ultrasound modulates the immune cell secretome in a time-dependent manner - ranging in ~0.1-3.6-fold changes in the concentration of a given cytokine compared to sham controls over 48 hours post-treatment (<i>e.g.</i> IL-1β, TNF-α, CX3CL1, CCL21). Further, we determine the general trend of a negative correlation between secreted cytokine concentration and viable ultrasound-assisted membrane permeability with negligible loss of cell viability. Taken together, the data presented here highlights the potential of microbubble-mediated focused ultrasound to viably enhance T-cell permeability and modulate key pro-immune pathways, offering a novel approach to augment targeted cellular therapies for solid tumors.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":null,"pages":null},"PeriodicalIF":5.7,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11534865/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142582548","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Elevation of serum neurofilament light-chain levels disclose possible occult progressive multifocal leukoencephalopathy and immune reconstitution syndrome in a patient receiving ozanimod: a case report. 一名接受奥扎莫德治疗的患者血清神经丝轻链水平升高,显示可能存在隐匿性进行性多灶性白质脑病和免疫重建综合征:病例报告。
IF 5.7 2区 医学
Frontiers in Immunology Pub Date : 2024-10-22 eCollection Date: 2024-01-01 DOI: 10.3389/fimmu.2024.1465678
Carlos Quintanilla-Bordás, David Gorriz, Laura Cubas-Núñez, Jéssica Castillo-Villalba, Joan Carreres-Polo, Bonaventura Casanova, Francisco Carlos Pérez-Miralles
{"title":"Elevation of serum neurofilament light-chain levels disclose possible occult progressive multifocal leukoencephalopathy and immune reconstitution syndrome in a patient receiving ozanimod: a case report.","authors":"Carlos Quintanilla-Bordás, David Gorriz, Laura Cubas-Núñez, Jéssica Castillo-Villalba, Joan Carreres-Polo, Bonaventura Casanova, Francisco Carlos Pérez-Miralles","doi":"10.3389/fimmu.2024.1465678","DOIUrl":"10.3389/fimmu.2024.1465678","url":null,"abstract":"<p><strong>Background: </strong>We report the first case of findings suggestive of progressive multifocal leukoencephalopathy and immune restitution syndrome (PML-IRIS) in a patient with multiple sclerosis receiving ozanimod preceded by an unexpected increase in the serum neurofilament light-chain (sNfL) levels.</p><p><strong>Case report: </strong>A 57-year-old-woman treated with ozanimod for the last 8 years presented, during surveillance MRI, with findings compatible with PML-IRIS. Overt clinical symptoms were absent. sNfL levels increased 4 months earlier and peaked at presentation. Lymphocyte count reached nadir of 330/mL at 8 months earlier.</p><p><strong>Conclusion: </strong>The case illustrates the utility of sNfL levels for PML surveillance in patients receiving immunosuppressors.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":null,"pages":null},"PeriodicalIF":5.7,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11535851/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142582522","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Gut microbiota: a crucial player in the combat against tuberculosis. 肠道微生物群:抗击结核病的关键角色。
IF 5.7 2区 医学
Frontiers in Immunology Pub Date : 2024-10-22 eCollection Date: 2024-01-01 DOI: 10.3389/fimmu.2024.1442095
Jie Lin, Dongli Chen, Yongen Yan, Jiang Pi, Junfa Xu, Lingming Chen, Biying Zheng
{"title":"Gut microbiota: a crucial player in the combat against tuberculosis.","authors":"Jie Lin, Dongli Chen, Yongen Yan, Jiang Pi, Junfa Xu, Lingming Chen, Biying Zheng","doi":"10.3389/fimmu.2024.1442095","DOIUrl":"10.3389/fimmu.2024.1442095","url":null,"abstract":"<p><p>The mammalian gastrointestinal tract quickly becomes densely populated with foreign microorganisms shortly after birth, thereby establishing a lifelong presence of a microbial community. These commensal gut microbiota serve various functions, such as providing nutrients, processing ingested compounds, maintaining gut homeostasis, and shaping the intestinal structure in the host. Dysbiosis, which is characterized by an imbalance in the microbial community, is closely linked to numerous human ailments and has recently emerged as a key factor in health prognosis. Tuberculosis (TB), a highly contagious and potentially fatal disease, presents a pressing need for improved methods of prevention, diagnosis, and treatment strategies. Thus, we aim to explore the latest developments on how the host's immune defenses, inflammatory responses, metabolic pathways, and nutritional status collectively impact the host's susceptibility to or resilience against <i>Mycobacterium tuberculosis</i> infection. The review addresses how the fluctuations in the gut microbiota not only affect the equilibrium of these physiological processes but also indirectly influence the host's capacity to resist <i>M. tuberculosis</i>. This work highlights the central role of the gut microbiota in the host-microbe interactions and provides novel insights for the advancement of preventative and therapeutic approaches against tuberculosis.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":null,"pages":null},"PeriodicalIF":5.7,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11534664/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142582529","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Prognostic role of serum cytokines level in non-small cell lung cancer patients with anti-PD-1 and chemotherapy combined treatment. 抗PD-1与化疗联合治疗非小细胞肺癌患者血清细胞因子水平的预后作用
IF 5.7 2区 医学
Frontiers in Immunology Pub Date : 2024-10-22 eCollection Date: 2024-01-01 DOI: 10.3389/fimmu.2024.1430301
Hongyu Liu, Chao Zhou, Haohua Jiang, Tianqing Chu, Runbo Zhong, Xueyan Zhang, Yinchen Shen, Baohui Han
{"title":"Prognostic role of serum cytokines level in non-small cell lung cancer patients with anti-PD-1 and chemotherapy combined treatment.","authors":"Hongyu Liu, Chao Zhou, Haohua Jiang, Tianqing Chu, Runbo Zhong, Xueyan Zhang, Yinchen Shen, Baohui Han","doi":"10.3389/fimmu.2024.1430301","DOIUrl":"10.3389/fimmu.2024.1430301","url":null,"abstract":"<p><strong>Background: </strong>Chemotherapy combined with PD-1 inhibitor treatment has revolutionized the standard of care for patients with NSCLC. However, the benefit is not universal, highlighting the need for precise prediction factors. Given their relationship with the immune system and non-invasive nature, serum cytokines are potential candidates for predicting the clinical effects of chemoimmunotherapy. Our study aims to evaluate the association of serum cytokines with the prognosis of patients with NSCLC treated with chemoimmunotherapy.</p><p><strong>Methods: </strong>Levels of 10 serum cytokines were detected in 60 NSCLC patients receiving chemotherapy plus PD-1 inhibitor-based treatment. Of these, dynamic samples from 19 patients were collected at baseline and after two treatment cycles. Their association with patients' clinicopathological characteristics, PFS and OS was described and investigated using survival analysis, cox regression and time-dependent ROC analysis. Preliminary evaluation of changes in cytokine levels associated with treatment response was conducted.</p><p><strong>Results: </strong>Patients with lower baseline levels of serum IL-6, IL-5, IL-8, TNF-α and IL-10 had longer PFS, while patients with higher levels of IL-4 had longer PFS. Patients with lower levels of serum IL-6, IL-8, IL-22, TNF-α and IL-10 had longer OS, while patients with higher levels of IL-4 had longer OS. Multivariate analysis suggested that higher IL-6 and IL-5 levels were associated with poorer PFS, and higher IL-6 levels were associated with dismal OS. Additionally, changes in serum cytokine levels could be associated with treatment response.</p><p><strong>Conclusion: </strong>Our study suggests that serum cytokines, specifically IL-6, IL-5, IL-8, TNF-α, IL-10, and IL-4, are potential prognostic factors for patients with NSCLC receiving chemotherapy plus PD-1 inhibitor treatment.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":null,"pages":null},"PeriodicalIF":5.7,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11534701/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142582537","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
The impact of trauma relevant concentrations of prostaglandin E2 on the anti-microbial activity of the innate immune system. 创伤相关浓度的前列腺素 E2 对先天免疫系统抗微生物活性的影响。
IF 5.7 2区 医学
Frontiers in Immunology Pub Date : 2024-10-22 eCollection Date: 2024-01-01 DOI: 10.3389/fimmu.2024.1401185
Thomas Nicholson, Antonio Belli, Janet M Lord, Jon Hazeldine
{"title":"The impact of trauma relevant concentrations of prostaglandin E<sub>2</sub> on the anti-microbial activity of the innate immune system.","authors":"Thomas Nicholson, Antonio Belli, Janet M Lord, Jon Hazeldine","doi":"10.3389/fimmu.2024.1401185","DOIUrl":"10.3389/fimmu.2024.1401185","url":null,"abstract":"<p><strong>Background: </strong>The mechanisms underlying the state of systemic immune suppression that develops following major trauma are poorly understood. A post-injury increase in circulating levels of prostaglandin E<sub>2</sub> (PGE<sub>2</sub>) has been proposed as a contributory factor, yet few studies have addressed how trauma influences PGE<sub>2</sub> biology.</p><p><strong>Methods: </strong>Blood samples from 95 traumatically-injured patients (injury severity score ≥8) were collected across the pre-hospital (≤2 hours), acute (4-12 hours) and subacute (48-72 hours) post-injury settings. Alongside <i>ex vivo</i> assessments of lipopolysaccharide (LPS)-induced cytokine production by monocytes, neutrophil reactive oxygen species production and phagocytosis, serum concentrations of PGE<sub>2</sub> and its scavenger albumin were measured, and the expression of enzymes and receptors involved in PGE<sub>2</sub> synthesis and signalling analysed. Leukocytes from trauma patients were treated with cyclooxygenase (COX) inhibitors (indomethacin or NS-398), or the protein kinase A inhibitor H89, to determine whether injury-induced immune suppression could be reversed by targeting the PGE<sub>2</sub> pathway. The effect that trauma relevant concentrations of PGE<sub>2</sub> had on the anti-microbial functions of neutrophils, monocytes and monocyte-derived macrophages (MDMs) from healthy controls (HC) was examined, as was the effect of PGE<sub>2</sub> on efferocytosis. To identify factors that may trigger PGE<sub>2</sub> production post-trauma, leukocytes from HC were treated with mitochondrial-derived damage associated molecular patterns (mtDAMPs) and COX-2 expression and PGE<sub>2</sub> generation measured.</p><p><strong>Results: </strong>PGE<sub>2</sub> concentrations peaked in blood samples acquired ≤2 hours post-injury and coincided with significantly reduced levels of albumin and impaired LPS-induced cytokine production by monocytes. Significantly higher COX-2 and phospholipase A<sub>2</sub> expression was detected in neutrophils and/or peripheral blood mononuclear cells isolated from trauma patients. Treatment of patient leukocytes with indomethacin, NS-398 or H89 enhanced LPS-induced cytokine production and neutrophil extracellular trap generation. Exposure to physiological concentrations of PGE<sub>2</sub> suppressed the anti-microbial activity of monocytes, neutrophils and MDMs of HC, but did not influence efferocytosis. In a formyl-peptide receptor-1 dependent manner, mtDAMP treatment significantly increased COX-2 protein expression in neutrophils and monocytes, which resulted in increased PGE<sub>2</sub> production.</p><p><strong>Conclusions: </strong>Physiological concentrations of PGE<sub>2</sub> suppress the anti-microbial activities of neutrophils, monocytes and MDMs. Targeting the PGE<sub>2</sub> pathway could be a therapeutic approach by which to enhance innate immune function post-injury.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":null,"pages":null},"PeriodicalIF":5.7,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11535544/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142582561","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
The complex role of immune cells in antigen presentation and regulation of T-cell responses in hepatocellular carcinoma: progress, challenges, and future directions. 肝细胞癌中免疫细胞在抗原递呈和 T 细胞反应调控中的复杂作用:进展、挑战和未来方向。
IF 5.7 2区 医学
Frontiers in Immunology Pub Date : 2024-10-22 eCollection Date: 2024-01-01 DOI: 10.3389/fimmu.2024.1483834
Jianbo Ning, Yutao Wang, Zijia Tao
{"title":"The complex role of immune cells in antigen presentation and regulation of T-cell responses in hepatocellular carcinoma: progress, challenges, and future directions.","authors":"Jianbo Ning, Yutao Wang, Zijia Tao","doi":"10.3389/fimmu.2024.1483834","DOIUrl":"10.3389/fimmu.2024.1483834","url":null,"abstract":"<p><p>Hepatocellular carcinoma (HCC) is a prevalent form of liver cancer that poses significant challenges regarding morbidity and mortality rates. In the context of HCC, immune cells play a vital role, especially concerning the presentation of antigens. This review explores the intricate interactions among immune cells within HCC, focusing on their functions in antigen presentation and the modulation of T-cell responses. We begin by summarizing the strategies that HCC uses to escape immune recognition, emphasizing the delicate equilibrium between immune surveillance and evasion. Next, we investigate the specific functions of various types of immune cells, including dendritic cells, natural killer (NK) cells, and CD8+ T cells, in the process of antigen presentation. We also examine the impact of immune checkpoints, such as cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and the pathways involving programmed cell death protein 1 (PD-1) and programmed death ligand 1 (PD-L1), on antigen presentation, while taking into account the clinical significance of checkpoint inhibitors. The review further emphasizes the importance of immune-based therapies, including cancer vaccines and CAR-T cell therapy, in improving antigen presentation. In conclusion, we encapsulate the latest advancements in research, propose future avenues for exploration, and stress the importance of innovative technologies and customized treatment strategies. By thoroughly analyzing the interactions of immune cells throughout the antigen presentation process in HCC, this review provides an up-to-date perspective on the field, setting the stage for new therapeutic approaches.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":null,"pages":null},"PeriodicalIF":5.7,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11534672/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142582559","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Comprehensive evaluation of clinical outcomes in hepatic epithelioid hemangioendothelioma subsets: insights from SEER Database and departmental cohort analysis. 全面评估肝上皮样血管内皮细胞瘤亚群的临床疗效:SEER数据库和部门队列分析的启示。
IF 5.7 2区 医学
Frontiers in Immunology Pub Date : 2024-10-22 eCollection Date: 2024-01-01 DOI: 10.3389/fimmu.2024.1491922
Bingchen Wang, Xiao Chen, Rongxuan Li, Bolun Ai, Feng Ye, Jianjun Zhao, Yefan Zhang, Zhen Huang, Zhiyu Li, Xinyu Bi, Hong Zhao, Dayong Cao, Jianqiang Cai, Jianguo Zhou, Tao Yan
{"title":"Comprehensive evaluation of clinical outcomes in hepatic epithelioid hemangioendothelioma subsets: insights from SEER Database and departmental cohort analysis.","authors":"Bingchen Wang, Xiao Chen, Rongxuan Li, Bolun Ai, Feng Ye, Jianjun Zhao, Yefan Zhang, Zhen Huang, Zhiyu Li, Xinyu Bi, Hong Zhao, Dayong Cao, Jianqiang Cai, Jianguo Zhou, Tao Yan","doi":"10.3389/fimmu.2024.1491922","DOIUrl":"10.3389/fimmu.2024.1491922","url":null,"abstract":"<p><strong>Background: </strong>Epithelioid hemangioendothelioma (EHE), is an uncommon, intermediate-grade malignant vascular tumor that can manifest in diverse organs, including the liver, lungs, and bones. Given its unique malignancy profile and rarity, there lacks a consensus on a standardized treatment protocol for EHE, particularly for hepatic epithelioid hemangioendothelioma (HEHE). This study aims to elucidate factors influencing the clinical prognosis of EHE by analyzing data from the SEER database, complemented with insights from a departmental cohort of 9 HEHE cases. Through this, we hope to shed light on potential clinical outcomes and therapeutic strategies for HEHE.</p><p><strong>Methods: </strong>Using SEER data from 22 registries, we analyzed 313 liver cancer patients with ICD-O-3 9130 and 9133 histology. Twelve variables were examined using Cox regression and mlr3 machine learning. Significant variables were identified and compared. Clinical data, imaging characteristics, and treatment methods of nine patients from our cohort were also presented.</p><p><strong>Result: </strong>In univariate and multivariate Cox regression analyses, Age, Sex, Year of diagnosis, Surgery of primary site, Chemotherapy, and Median household income were closely related to survival outcomes. Among the ten survival-related machine learning models, CoxPH, Flexible, Mboost, and Gamboost stood out based on Area Under the Curve(AUC), Decision Curve Analysis(DCA), and Calibration Curve Metrics. In the feature importance analysis of these four selected models, Age and Surgery of primary site were consistently identified as the most critical factors influencing prognosis. Additionally, the clinical data of nine patients from our cohort not only demonstrated unique imaging characteristics of HEHE but also underscored the importance of surgical intervention.</p><p><strong>Conclusion: </strong>For patients with resectable HEHE, surgical treatment is currently a highly important therapeutic approach.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":null,"pages":null},"PeriodicalIF":5.7,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11534872/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142582491","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Treatment of refractory immune-mediated necrotizing myopathy with efgartigimod. 用依加替莫德治疗难治性免疫介导的坏死性肌病。
IF 5.7 2区 医学
Frontiers in Immunology Pub Date : 2024-10-22 eCollection Date: 2024-01-01 DOI: 10.3389/fimmu.2024.1447182
MengTing Yang, JingChu Yuan, YiKang Wang, HongJun Hao, Wei Zhang, ZhaoXia Wang, Yun Yuan, YaWen Zhao
{"title":"Treatment of refractory immune-mediated necrotizing myopathy with efgartigimod.","authors":"MengTing Yang, JingChu Yuan, YiKang Wang, HongJun Hao, Wei Zhang, ZhaoXia Wang, Yun Yuan, YaWen Zhao","doi":"10.3389/fimmu.2024.1447182","DOIUrl":"10.3389/fimmu.2024.1447182","url":null,"abstract":"<p><strong>Objective: </strong>We aimed to explore the efficacy and safety of efgartigimod in patients with refractory immune-mediated necrotizing myopathy (IMNM).</p><p><strong>Methods: </strong>This open-label pilot observational study included seven patients with refractory IMNM, all of whom received intravenous efgartigimod treatment. The clinical response was assessed after 4 weeks of efgartigimod treatment according to the 2016 American College of Rheumatology-European League Against Rheumatism response criteria for adult idiopathic inflammatory myopathy. Serum levels of immunoglobulin as well as anti-signal recognition particle (SRP) and anti-3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR) antibodies were measured using enzyme-linked immunosorbent assays and commercial line immunoblot assays. Safety assessments included evaluations of adverse events and severe adverse events.</p><p><strong>Results: </strong>The seven patients with refractory IMNM included five cases with anti-HMGCR antibodies and two cases within anti-SRP antibodies. Four of the seven patients achieved clinical responses. The total improvement score for the responders at 4 weeks were 32.5, 40.0, 47.5, and 70.0, and those at 8 weeks were 27.5, 47.5, 57.5, and 70.0. In comparison to the responsive patients, the non-responsive patients had longer durations [8 (-) versus 2 (1-5) years, <i>P</i> = 0.03], and more chronic myopathic features by muscle biopsy (67% versus 0%, <i>P</i> = 0.046). Serum immunoglobulin G levels (11.2 ± 2.5 versus 5.7 ± 2.5, <i>P</i> = 0.007) and anti-HMGCR/SRP antibody levels (97.2 ± 6.9 versus 41.8 ± 16.8, <i>P</i> = 0.002) were decreased after treatment compared with baseline levels. Adverse events were reported in one of the seven patients, who showed mild headache.</p><p><strong>Conclusions: </strong>Despite its small size, our study demonstrated that promoting the degradation of endogenous immunoglobulin G may be effective for patients with IMNM. Efgartigimod may be a promising option for cases of refractory IMNM to shorten duration and minimize chronic myopathic features.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":null,"pages":null},"PeriodicalIF":5.7,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11534618/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142582571","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Peripheral immune profiling of soft tissue sarcoma: perspectives for disease monitoring. 软组织肉瘤的外周免疫分析:疾病监测的前景。
IF 5.7 2区 医学
Frontiers in Immunology Pub Date : 2024-10-21 eCollection Date: 2024-01-01 DOI: 10.3389/fimmu.2024.1391840
Jani Sofia Almeida, Luana Madalena Sousa, Patrícia Couceiro, Tânia Fortes Andrade, Vera Alves, António Martinho, Joana Rodrigues, Ruben Fonseca, Paulo Freitas-Tavares, Manuel Santos-Rosa, José Manuel Casanova, Paulo Rodrigues-Santos
{"title":"Peripheral immune profiling of soft tissue sarcoma: perspectives for disease monitoring.","authors":"Jani Sofia Almeida, Luana Madalena Sousa, Patrícia Couceiro, Tânia Fortes Andrade, Vera Alves, António Martinho, Joana Rodrigues, Ruben Fonseca, Paulo Freitas-Tavares, Manuel Santos-Rosa, José Manuel Casanova, Paulo Rodrigues-Santos","doi":"10.3389/fimmu.2024.1391840","DOIUrl":"10.3389/fimmu.2024.1391840","url":null,"abstract":"<p><p>Studying the tumor microenvironment and surrounding lymph nodes is the main focus of current immunological research on soft tissue sarcomas (STS). However, due to the restricted opportunity to examine tumor samples, alternative approaches are required to evaluate immune responses in non-surgical patients. Therefore, the purpose of this study was to evaluate the peripheral immune profile of STS patients, characterize patients accordingly and explore the impact of peripheral immunotypes on patient survival. Blood samples were collected from 55 STS patients and age-matched healthy donors (HD) controls. Deep immunophenotyping and gene expression analysis of whole blood was analyzed using multiparametric flow cytometry and real-time RT-qPCR, respectively. Using xMAP technology, proteomic analysis was also carried out on plasma samples. Unsupervised clustering analysis was used to classify patients based on their immune profiles to further analyze the impact of peripheral immunotypes on patient survival. Significant differences were found between STS patients and HD controls. It was found a contraction of B cells and CD4 T cells compartment, along with decreased expression levels of ICOSLG and CD40LG; a major contribution of suppressor factors, as increased frequency of M-MDSC and memory Tregs, increased expression levels of ARG1, and increased plasma levels of IL-10, soluble VISTA and soluble TIMD-4; and a compromised cytotoxic potential associated with NK and CD8 T cells, namely decreased frequency of CD56<sup>dim</sup> NK cells, and decreased levels of PRF1, GZMB, and KLRK1. In addition, the patients were classified into three peripheral immunotype groups: \"immune-high,\" \"immune-intermediate,\" and \"immune-low.\" Furthermore, it was found a correlation between these immunotypes and patient survival. Patients classified as \"immune-high\" exhibited higher levels of immune-related factors linked to cytotoxic/effector activity and longer survival times, whereas patients classified as \"immune-low\" displayed higher levels of immune factors associated with immunosuppression and shorter survival times. In conclusion, it can be suggested that STS patients have a compromised systemic immunity, and the correlation between immunotypes and survival emphasizes the importance of studying peripheral blood samples in STS. Assessing the peripheral immune response holds promise as a useful method for monitoring and forecasting outcomes in STS.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":null,"pages":null},"PeriodicalIF":5.7,"publicationDate":"2024-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11536262/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142582568","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Animal models of membranous nephropathy: more choices and higher similarity. 膜性肾病的动物模型:选择更多、相似度更高。
IF 5.7 2区 医学
Frontiers in Immunology Pub Date : 2024-10-21 eCollection Date: 2024-01-01 DOI: 10.3389/fimmu.2024.1412826
Ying Pan, Si Chen, Lin Wu, Changying Xing, Huijuan Mao, Hongwei Liang, Yanggang Yuan
{"title":"Animal models of membranous nephropathy: more choices and higher similarity.","authors":"Ying Pan, Si Chen, Lin Wu, Changying Xing, Huijuan Mao, Hongwei Liang, Yanggang Yuan","doi":"10.3389/fimmu.2024.1412826","DOIUrl":"10.3389/fimmu.2024.1412826","url":null,"abstract":"<p><p>Membranous nephropathy (MN) is an antibody-mediated autoimmune glomerular disease in which PLA2R1 is the main autoantibody. It has become the most common cause of adult nephrotic syndrome, and about one-third of patients can progress to end-stage kidney disease, but its pathogenesis is still unclear. Animal models can be used as suitable tools to study the pathogenesis and treatment of MN. The previous Heymann nephritis rat model and C-BSA animal model are widely used to study the pathogenesis of MN. However, the lack of target antigen expression in podocytes of model animals (especially rodents) restricts the application. In recent years, researchers constructed animal models of antigen-specific MN, such as THSD7A, PLA2R1, which more truly simulate the pathogenesis and pathological features of MN and provide more choices for the follow-up researchers. When selecting these MN models, we need to consider many aspects, including cost, difficulty of model preparation, labor force, and whether the final model can answer the research questions. This review is to comprehensively evaluate the mechanism, advantages and disadvantages and feasibility of existing animal models, and provide new reference for the pathogenesis and treatment of MN.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":null,"pages":null},"PeriodicalIF":5.7,"publicationDate":"2024-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11532550/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142577441","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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