Immunotherapy advances最新文献_第2页

Knowledge-based immune-therapeutic advances for transplantation and cancer. 基于知识的移植和癌症免疫治疗进展。

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Immunotherapy advances Pub Date : 2025-03-28 eCollection Date: 2025-01-01 DOI: 10.1093/immadv/ltaf014

Elizabeth Simpson

{"title":"Knowledge-based immune-therapeutic advances for transplantation and cancer.","authors":"Elizabeth Simpson","doi":"10.1093/immadv/ltaf014","DOIUrl":"10.1093/immadv/ltaf014","url":null,"abstract":"Increased knowledge about immune responses to what is perceived as 'foreign' or 'non-self' has revealed extraordinary levels of complexity. Research uncovering these has the potential to optimise immunotherapy. Remarkable progress has been made in transplantation leading to much less acute rejection and a very significant increase in long-term survival. These and other beneficial results have been achieved by stepwise advances, using combinations of less toxic chemotherapies with biological immunosuppressive agents alongside innovatory surgical skills. However, rejection is the default pathway for entities deemed 'foreign', including mistaken suspects like autoantigens. For tumour immunotherapy the identification of bona fide tumour antigens recognised by B and/or T cell receptors has mushroomed but has yet to be optimised to take into account mutations leading to tumour evasion. We are now at the beginning of a road that looks more hopeful by being informed of the complexities. Basic and translational research between the late 1960s and now have yielded an extraordinarily rich harvest of new knowledge. More is to come, further insight is needed and new paradigms explored.","PeriodicalId":73353,"journal":{"name":"Immunotherapy advances","volume":"5 1","pages":"ltaf014"},"PeriodicalIF":4.1,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12216359/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144556088","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Lag3 and PD-1 pathways preferentially regulate NFAT-dependent TCR signalling programmes during early CD4⁺ T cell activation. Lag3和PD-1通路在早期CD4+ T细胞活化过程中优先调节nfat依赖性TCR信号程序。

IF 4.1

Immunotherapy advances Pub Date : 2025-03-28 eCollection Date: 2025-01-01 DOI: 10.1093/immadv/ltaf015

Lozan Sheriff, Alastair Copland, David A J Lecky, Reygn Done, Lorna S George, Emma K Jennings, Sophie Rouvray, Thomas A E Elliot, Elizabeth S Jinks, Lalit Pallan, David Bending

{"title":"Lag3 and PD-1 pathways preferentially regulate NFAT-dependent TCR signalling programmes during early CD4+ T cell activation.","authors":"Lozan Sheriff, Alastair Copland, David A J Lecky, Reygn Done, Lorna S George, Emma K Jennings, Sophie Rouvray, Thomas A E Elliot, Elizabeth S Jinks, Lalit Pallan, David Bending","doi":"10.1093/immadv/ltaf015","DOIUrl":"https://doi.org/10.1093/immadv/ltaf015","url":null,"abstract":"Introduction: Lag3 and PD-1 are immune checkpoints that regulate T cell responses and are current immunotherapy targets. Yet how they function to control early stages of CD4+ T cell activation remains unclear.Methods: Here, we show that the PD-1 and Lag3 pathways exhibit layered control of the early CD4+ T cell activation process, with the effects of Lag3 more pronounced in the presence of PD-1 pathway co-blockade (CB). RNA sequencing revealed that CB drove an early NFAT-dependent transcriptional profile, including promotion of ICOShi T follicular helper cell differentiation.Results: NFAT pathway inhibition abolished CB-induced upregulation of NFAT-dependent co-receptors ICOS and OX40, whilst unaffecting the NFAT-independent gene Nr4a1. Mechanistically, Lag3 and PD-1 pathways functioned additively to regulate the duration of T cell receptor signals during CD4+ T cell re-activation. Phenotypic changes in peripheral blood CD4+ T cells in humans on anti-Lag3 and anti-PD-1 combination therapy revealed upregulation of genes encoding ICOS and OX40 on distinct CD4+ T cell subsets, highlighting the potential translational relevance of our findings.Conclusion: Our data therefore reveal that PD-1 and Lag3 pathways converge to additively regulate TCR signal duration and may preferentially control NFAT-dependent transcriptional activity during early CD4+ T cell re-activation.","PeriodicalId":73353,"journal":{"name":"Immunotherapy advances","volume":"5 1","pages":"ltaf015"},"PeriodicalIF":4.1,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12066006/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144037625","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Abnormal glucose and lipid metabolism promotes disrupted differentiation of T and B cell subsets in Behçet's disease. 糖脂代谢异常促进behaperet病中T细胞和B细胞亚群分化中断。

IF 4.1

Immunotherapy advances Pub Date : 2025-03-24 eCollection Date: 2025-01-01 DOI: 10.1093/immadv/ltaf010

Minghao Li, Ping Li, Xin Wang, Lijie Wang, Guanmin Gao, Guosheng Jiang, Tingting Liu, Wei Lin

{"title":"Abnormal glucose and lipid metabolism promotes disrupted differentiation of T and B cell subsets in Behçet's disease.","authors":"Minghao Li, Ping Li, Xin Wang, Lijie Wang, Guanmin Gao, Guosheng Jiang, Tingting Liu, Wei Lin","doi":"10.1093/immadv/ltaf010","DOIUrl":"https://doi.org/10.1093/immadv/ltaf010","url":null,"abstract":"Introduction: Behçet's disease (BD) is a chronic, systemic inflammatory condition characterized by recurrent immune dysregulation.Materials & methods: This study conducted a comprehensive analysis of immune cell subsets, metabolic markers, and their interplay in BD patients. Using multiparametric flow cytometry, we identified elevated Th1 cells, senescent CD8+ T cells, and abnormal B cell activation as hallmarks of the chronic inflammatory state in BD.Results: Despite immunotherapy, innate immune activation persisted, with increased mature NK cells, γδT1 cells, and conventional dendritic cells (cDCs), alongside reduced plasmacytoid dendritic cells (pDCs). Elevated glucose (GLU) and triacylglycerol (TAG) levels in BD patients correlated with increased Th1 cells, functional CD8+ T cells, and B cell activation. In vitro experiments demonstrated that GLU and TAG promote Th1 differentiation, CD8+ T cell activation, and B cell antibody production, revealing their role as drivers of immune dysregulation.Conclusion: These findings underscore the intricate relationship between metabolic dysregulation and immune dysfunction in BD, highlighting potential diagnostic and therapeutic targets. Our study provides critical insights into BD pathogenesis, offering a foundation for optimizing disease management and monitoring immune and metabolic markers for improved patient outcomes.","PeriodicalId":73353,"journal":{"name":"Immunotherapy advances","volume":"5 1","pages":"ltaf010"},"PeriodicalIF":4.1,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12036013/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144054531","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Intra-tumoural RAMP1+ B cells promote resistance to neoadjuvant anti-PD-1-based therapy in oesophageal squamous cell carcinoma. 肿瘤内RAMP1+ B细胞促进食管鳞状细胞癌对新辅助抗pd -1治疗的耐药性。

IF 4.1

Immunotherapy advances Pub Date : 2025-03-22 eCollection Date: 2025-01-01 DOI: 10.1093/immadv/ltaf012

Hongyu Zhang, Yuchen Zhang, Pingjing Zhou, Yifan Guo, Liqun Jiang, Jie Gu

{"title":"Intra-tumoural RAMP1+ B cells promote resistance to neoadjuvant anti-PD-1-based therapy in oesophageal squamous cell carcinoma.","authors":"Hongyu Zhang, Yuchen Zhang, Pingjing Zhou, Yifan Guo, Liqun Jiang, Jie Gu","doi":"10.1093/immadv/ltaf012","DOIUrl":"10.1093/immadv/ltaf012","url":null,"abstract":"Introduction: The application of neoadjuvant immunotherapy in oesophageal squamous cell carcinoma (ESCC) reactivates anti-tumour immune responses and prolong postoperative survival. However, due to the heterogeneity of tumour microenvironment, limited patients have achieved pathological regression after treatment. The dual roles of B cells were recently highlighted in ESCC. The study aimed to investigate the role of B cell subclusters and the upstream signalling of B cell differentiation in ESCC resistant to immunotherapy.Methods: Single-cell RNA sequencing was employed for ESCC specimens with distinct responses to neoadjuvant immunotherapy to map the landscape of intra-tumoural B cells.Results: A novel subset of neuropeptide receptor, receptor activity-modifying protein 1 (RAMP1) positive B cells was revealed to accumulate in ESCC that is resistant to neoadjuvant immunotherapy. Stimulated by nociceptor neurons secreting calcitonin gene-related peptide (CGRP), RAMP1(+) B cells exhibit an immunosuppressive phenotype. The elevated secretion of immune-regulating cytokines by RAMP1(+) B cells blunts the cytotoxicity of Cluster of Differentiation (CD)8(+) T cell and leads to tumour immune evasion. A combination of RAMP1 blocker and anti-Programmed cell death protein (PD)-1 therapies synergistically reinvigorated anti-tumour immunity, reducing tumour progression in vitro.Conclusion: The study suggests that RAMP1(+) B cells play a critical role in mediating resistance to neoadjuvant immunotherapy in ESCC. Targeting the CGRP-RAMP axis remodels B cells and enhance the efficacy of current immunotherapies, providing new strategies for overcoming treatment resistance.","PeriodicalId":73353,"journal":{"name":"Immunotherapy advances","volume":"5 1","pages":"ltaf012"},"PeriodicalIF":4.1,"publicationDate":"2025-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12084762/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144095714","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Implementing adjuvant immunotherapy following radical chemoradiotherapy for stage III non-small-cell lung cancer in UK clinical practice-Are the PACIFIC trial outcomes achievable in the real world? 在英国临床实践中，在根治性放化疗后对III期非小细胞肺癌实施辅助免疫治疗- PACIFIC试验结果在现实世界中可以实现吗？

IF 4.1

Immunotherapy advances Pub Date : 2025-03-17 eCollection Date: 2025-01-01 DOI: 10.1093/immadv/ltaf011

Radwa Fawzy Ahmed, Paul Fenton, Adityanarayan Bhatnagar, Victoria Wood, Andrew Bates

{"title":"Implementing adjuvant immunotherapy following radical chemoradiotherapy for stage III non-small-cell lung cancer in UK clinical practice-Are the PACIFIC trial outcomes achievable in the real world?","authors":"Radwa Fawzy Ahmed, Paul Fenton, Adityanarayan Bhatnagar, Victoria Wood, Andrew Bates","doi":"10.1093/immadv/ltaf011","DOIUrl":"https://doi.org/10.1093/immadv/ltaf011","url":null,"abstract":"Introduction: PACIFIC trial demonstrates improved progression-free survival (PFS) and overall survival (OS) in patients with locally advanced non-small-cell lung cancer (NSCLC) treated with platinum-based concurrent chemoradiotherapy (CRT) and adjuvant Durvalumab immunotherapy.Methods: We retrospectively reviewed 72 consecutive patients with locally advanced NSCLC treated with platinum-based concurrent CRT, who were potentially eligible for adjuvant Durvaluamb treatment (PDL1 ≥1% or inadequate). We analysed PFS, OS, treatment toxicity, and the impact of PDL1 on these outcomes.Results: The cohort median follow-up was 20 months. Fifty-five patients received adjuvant Durvalumab. The median OS (mOS) has not been reached. OS at 24 months was 67.8% for patients received Durvalumab. The median PFS (mPFS) for patients received Durvalumab was 30 months. PDL1 status (1-49% vs. ≥50%) did not affect outcome in our cohort. Sixteen patients stopped Durvalumab due to immune toxicity. At 24 months, 49% of these patients were still alive versus 76% of the patients who completed 12 months of treatment. The mOS for patients who stopped Durvalumab due to immune toxicity was 16 months, P = .0032. Seventeen patients did not receive adjuvant treatment due to insufficient performance status following CRT and mOS was 6 months.Conclusions: Our real-world experience demonstrates possibility to achieve similar outcomes to PACIFIC trial. PDL1 status did not affect clinical outcome in our cohort. Patients who stopped adjuvant Durvalumab treatment due to toxicity and those who were not deemed suitable to proceed with adjuvant Durvalumab after CRT, had poorer outcomes. This indicates that careful case selection remains essential.","PeriodicalId":73353,"journal":{"name":"Immunotherapy advances","volume":"5 1","pages":"ltaf011"},"PeriodicalIF":4.1,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12076069/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144082578","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Development and evaluation of two whole-blood flow cytometry protocols for monitoring patients treated with JAK inhibitors. 开发和评估两种全血流式细胞术方案，用于监测接受JAK抑制剂治疗的患者。

IF 4.1

Immunotherapy advances Pub Date : 2025-03-12 eCollection Date: 2025-01-01 DOI: 10.1093/immadv/ltaf006

Louis Waeckel, Chloé Talon, Mathilde Barrau, Anne-Emmanuelle Berger, Xavier Roblin, Stéphane Paul

{"title":"Development and evaluation of two whole-blood flow cytometry protocols for monitoring patients treated with JAK inhibitors.","authors":"Louis Waeckel, Chloé Talon, Mathilde Barrau, Anne-Emmanuelle Berger, Xavier Roblin, Stéphane Paul","doi":"10.1093/immadv/ltaf006","DOIUrl":"https://doi.org/10.1093/immadv/ltaf006","url":null,"abstract":"Introduction: The clinical efficacy of Janus kinase inhibitors (JAKinibs) is highly variable and their safety profiles are poorly understood.Methods: We established two flow cytometry panels for the assessment of two promising leukocyte biomarkers: signal transducer and activator of transcription (STAT) phosphorylation and cytokine receptor expression. We evaluated the first panel, which assesses phosphorylation levels for STAT1, STAT3, and STAT5 after cytokine stimulation, with or without in vitro pretreatment with JAKinibs, in 10 healthy donors. We then evaluated the second panel, which assesses cytokine receptor expression on T cells and B cells, in five healthy donors.Results: Stimulation with interleukin (IL)-2 or IL-7 increased STAT5 phosphorylation in T cells but not in B cells or monocytes. IL-6 stimulation induced STAT3 phosphorylation in monocytes and CD4 T cells and, to a lesser extent, in CD8 T cells, but not in B cells. IL-21 stimulation led to STAT3 phosphorylation in T cells and, to a lesser extent, in B cells, but not in monocytes. Interferon-α stimulation increased STAT1 phosphorylation in all cell types. STAT phosphorylation levels were lower after pretreatment with JAKinibs. A dose-response curve was plotted, confirming the correlation between JAKinib concentration and STAT phosphorylation inhibition. The second panel showed that each cell type displayed a distinct pattern of cytokine receptors expression, and that this pattern might be modified by in vitro treatment with JAKinibs.Conclusion: This preliminary study confirms the utility of flow cytometry for monitoring the biological effects of JAKinibs. Further studies on treated patients are now required to evaluate the clinical value of these two flow cytometry panels.","PeriodicalId":73353,"journal":{"name":"Immunotherapy advances","volume":"5 1","pages":"ltaf006"},"PeriodicalIF":4.1,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12012447/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144037622","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Therapeutic targeting of tumour-associated macrophage receptors. 肿瘤相关巨噬细胞受体的靶向治疗。

IF 4.1

Immunotherapy advances Pub Date : 2025-03-11 eCollection Date: 2025-01-01 DOI: 10.1093/immadv/ltaf009

Rosa Gomes Alves Martins, Mehmet M Tekin, Mark S Cragg, Ali Roghanian

引用次数: 0

M2 macrophages promote IL-10⁺B-cell production and alleviate asthma in mice. M2巨噬细胞促进IL-10+ b细胞生成，减轻小鼠哮喘。

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Immunotherapy advances Pub Date : 2025-03-10 eCollection Date: 2025-01-01 DOI: 10.1093/immadv/ltaf007

Baichao Yu, Xueqi Wang, Yongkun Zheng, Wenjun Wang, Xiaoqin Cheng, Yue Cao, Mingxing Wei, Ying Fu, Yiwei Chu, Luman Wang

{"title":"M2 macrophages promote IL-10+B-cell production and alleviate asthma in mice.","authors":"Baichao Yu, Xueqi Wang, Yongkun Zheng, Wenjun Wang, Xiaoqin Cheng, Yue Cao, Mingxing Wei, Ying Fu, Yiwei Chu, Luman Wang","doi":"10.1093/immadv/ltaf007","DOIUrl":"https://doi.org/10.1093/immadv/ltaf007","url":null,"abstract":"Introduction: B cells have a central regulatory role in various diseases. While macrophages are found in the disease microenvironment and interact with tissue and diverse immune cells, their relationship with B cells remains poorly explored.Methods: This study used an asthma animal model and macrophage depletion and demonstrated a significant exacerbation of asthma symptoms upon macrophage removal, coupled with a marked reduction in IL-10+ B-cell expression.Results: Further analysis revealed that the macrophages interacting with IL-10+ B cells in the asthma microenvironment were of the M2 subtype. Furthermore, our sequencing data indicated a potential mechanism wherein M2 macrophages promote IL-10+ B-cell activity through the TGF-β pathway and oxidative phosphorylation pathways.Conclusion: These findings suggest that M2 macrophages modulate IL-10+ B cells, ultimately mitigating asthma symptoms in mouse models.","PeriodicalId":73353,"journal":{"name":"Immunotherapy advances","volume":"5 1","pages":"ltaf007"},"PeriodicalIF":4.1,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12059559/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144044210","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

CTLA-4-two pathways to anti-tumour immunity? ctla -4-两种抗肿瘤免疫途径？

IF 4.1

Immunotherapy advances Pub Date : 2025-03-07 eCollection Date: 2025-01-01 DOI: 10.1093/immadv/ltaf008

Frank J Ward, Paul T Kennedy, Farah Al-Fatyan, Lekh N Dahal, Rasha Abu-Eid

{"title":"CTLA-4-two pathways to anti-tumour immunity?","authors":"Frank J Ward, Paul T Kennedy, Farah Al-Fatyan, Lekh N Dahal, Rasha Abu-Eid","doi":"10.1093/immadv/ltaf008","DOIUrl":"https://doi.org/10.1093/immadv/ltaf008","url":null,"abstract":"Immune checkpoint inhibitor (ICI) therapies have revolutionized cancer therapy and improved patient outcomes in a range of cancers. ICIs enhance anti-tumour immunity by targeting the inhibitory checkpoint receptors CTLA-4, PD-1, PD-L1, and LAG-3. Despite their success, efficacy, and tolerance vary between patients, raising new challenges to improve these therapies. These could be addressed by the identification of robust biomarkers to predict patient outcome and a more complete understanding of how ICIs affect and are affected by the tumour microenvironment (TME). Despite being the first ICIs to be introduced, anti-CTLA-4 antibodies have underperformed compared with antibodies that target the PD-1/PDL-1 axis. This is due to the complexity regarding their precise mechanism of action, with two possible routes to efficacy identified. The first is a direct enhancement of effector T-cell responses through simple blockade of CTLA-4-'releasing the brakes', while the second requires prior elimination of regulatory T cells (TREG) to allow emergence of T-cell-mediated destruction of tumour cells. We examine evidence indicating both mechanisms exist but offer different antagonistic characteristics. Further, we investigate the potential of the soluble isoform of CTLA-4, sCTLA-4, as a confounding factor for current therapies, but also as a therapeutic for delivering antigen-specific anti-tumour immunity.","PeriodicalId":73353,"journal":{"name":"Immunotherapy advances","volume":"5 1","pages":"ltaf008"},"PeriodicalIF":4.1,"publicationDate":"2025-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12012449/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144044273","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Lung immune challenge study protocol: controlled exposure to inhaled resiquimod (R848) to study mechanisms of inflammation. 肺免疫攻击研究方案：受控暴露于吸入雷昔莫特（R848）以研究炎症机制。

IF 4.1

Immunotherapy advances Pub Date : 2025-02-24 eCollection Date: 2025-01-01 DOI: 10.1093/immadv/ltaf005

Akhilesh Jha, Marie Fisk, Jamie Forrester, Jacqui Galloway, Jade Joseph, Robyn Staples, Karl P Sylvester

{"title":"Lung immune challenge study protocol: controlled exposure to inhaled resiquimod (R848) to study mechanisms of inflammation.","authors":"Akhilesh Jha, Marie Fisk, Jamie Forrester, Jacqui Galloway, Jade Joseph, Robyn Staples, Karl P Sylvester","doi":"10.1093/immadv/ltaf005","DOIUrl":"10.1093/immadv/ltaf005","url":null,"abstract":"This study aims to develop a human lung immune challenge model using inhaled Resiquimod (R848), a Toll-like receptor 7/8 agonist, to investigate inflammatory mechanisms involved in the human respiratory mucosa in health and disease. This approach seeks to induce innate immune anti-viral responses in the lungs and blood, with a suitable dose of inhaled R848 that is clinically tolerable. The study will include healthy volunteers and individuals with asthma. The primary outcome is a change in CXCL10, a biomarker representative of anti-viral responses, at 24 hours post-exposure. Secondary outcomes include changes in lung function, physiological parameters, and inflammatory markers, including C-reactive protein and eosinophil counts. This trial involves a single ascending dose, randomized, single-blind, placebo-controlled design. Participants will receive R848 via nebulization in escalating doses from 0.1 to 100 µg/ml or saline placebo. Safety assessments include spirometry, vital signs, and blood samples to monitor systemic and lung-specific immune responses. The study will contribute to understanding immune pathways in asthma and provide a platform for testing novel anti-inflammatory therapeutics. The protocol has been approved by relevant ethics committees and will be disseminated via peer-reviewed publications and open-access data repositories.","PeriodicalId":73353,"journal":{"name":"Immunotherapy advances","volume":"5 1","pages":"ltaf005"},"PeriodicalIF":4.1,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11976720/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143812981","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0