Frontiers in Immunology最新文献

{"title":"Placental malaria infection is associated with downregulation of STAT-6 and ANG-1 in decidual macrophages.","authors":"Fred Owino, Caroline Kijogi, Omu Anzala, Edwin Walong, Obiero Jael, Steven G Nyanjom, Agola Lelo Eric, Bernard N Kanoi, Jesse Gitaka","doi":"10.3389/fimmu.2025.1497936","DOIUrl":"https://doi.org/10.3389/fimmu.2025.1497936","url":null,"abstract":"<p><strong>Introduction: </strong>Macrophages play a crucial immunological role in maintaining pregnancy. Placental malaria infection may cause dysfunction in decidual macrophages which then culminates in the associated pregnancy complications. Here, we determined the influence of placental malaria on decidual macrophages, by assessing their distribution based on their unique phenotypes, and examining their expression levels of transcription factors as well as angiogenic factors, in placentas from women living in a malaria-endemic area.</p><p><strong>Methods: </strong>We compared these macrophage parameters in placentas from malaria infected women to those from the uninfected women. Placentas were collected upon delivery and malaria infection determined by histology together with PCR from dry blood spots obtained from placental blood. Following enzymatic dissociation of placental tissue, immune cells were enriched from the total population of placental cells by density centrifugation. Macrophage phenotypic characteristics were then analyzed from the placental immune cells by flow cytometry. The expression of surface markers CD68, CD80, CD86, CD163, CD206, and CD209, was used to delineate the macrophage populations. For gene expression profiling, macrophages were isolated from the placental immune cells and the expression level of transcription factors <i>STAT-1, IRF-5, STAT-6, c-Maf</i> and angiogenic factors <i>ANG-1, ANG-2</i> and <i>VEGF</i> determined by qPCR.</p><p><strong>Results and discussion: </strong>We found no difference in the total macrophage populations and M1 and M2 macrophage profiles between uninfected and infected placentas, however, M2 macrophages were significantly higher compared to their M1 counterparts regardless of infection status. Notably, the gene expression levels of the transcription factor <i>STAT-6</i> and angiogenic factor <i>ANG-1</i> were significantly lower in infected placentas. These findings provide a basis for further understanding of the role of placental macrophages in placental malaria pathogenesis. Analysis of the functional consequences of these observations is needed to determine if these factors can be explored to reprogram macrophage polarization to desired state.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"16 ","pages":"1497936"},"PeriodicalIF":5.7,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11850307/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143500548","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}

{"title":"Six events that shaped antibody approvals in oncology.","authors":"Suman Paul, Shibin Zhou","doi":"10.3389/fimmu.2025.1533796","DOIUrl":"10.3389/fimmu.2025.1533796","url":null,"abstract":"<p><p>A little over twenty-five years ago, the European Medicines Agency (EMA) and the Food and Drug Administration (FDA) approved the chimeric antibody rituximab which fundamentally altered the landscape of anti-cancer drugs. While only a few antibodies were approved in the immediate years that followed the rituximab approval, the last decade saw a wave of antibody-drug approvals in the oncology arena. In the last three years, the EMA and FDA greenlighted eighteen antibodies, the majority of them designed in the formats of antibody-drug conjugates (ADC) and bispecific antibodies (BsAb). While the use of ADC and BsAb formats and the current rapid pace of approvals appear routine and almost inevitable, such progress was thought to be quite improbable in the early days of therapeutic antibody development. To understand how we arrived at the current state of antibody development in oncology, we focus on six monumental events that shaped antibody approvals over the last two and half decades. We examine the circumstances that led to the approval of rituximab and trastuzumab, the first successful antibodies for the treatment of hematologic and solid cancers. We detail the generation of the ADC and BsAb formats that dramatically augmented antibody-mediated precision cytotoxicity. Finally, we explore the development of ipilimumab, the first immune checkpoint-inhibiting antibody that activates the immune system to kill cancer cells, and the discovery that allowed the use of checkpoint inhibitors across all cancer types based on the presence of genetic markers. Revisiting these key events provides critical insights into the process of antibody development in oncology.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"16 ","pages":"1533796"},"PeriodicalIF":5.7,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11847691/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143491649","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}

{"title":"Non-small cell lung cancer and the tumor microenvironment: making headway from targeted therapies to advanced immunotherapy.","authors":"Anna De Lucia, Lucia Mazzotti, Anna Gaimari, Matteo Zurlo, Roberta Maltoni, Claudio Cerchione, Sara Bravaccini, Angelo Delmonte, Lucio Crinò, Patricia Borges de Souza, Luigi Pasini, Fabio Nicolini, Fabrizio Bianchi, Manel Juan, Hugo Calderon, Chiara Magnoni, Luca Gazzola, Paola Ulivi, Massimiliano Mazza","doi":"10.3389/fimmu.2025.1515748","DOIUrl":"10.3389/fimmu.2025.1515748","url":null,"abstract":"<p><p>Over the past decades, significant progress has been made in the understanding of non-small cell lung cancer (NSCLC) biology and tumor progression mechanisms, resulting in the development of novel strategies for early detection and wide-ranging care approaches. Since their introduction, over 20 years ago, targeted therapies with tyrosine kinase inhibitors (TKIs) have revolutionized the treatment landscape for NSCLC. Nowadays, targeted therapies remain the gold standard for many patients, but still they suffer from many adverse effects, including unexpected toxicity and intrinsic acquired resistance mutations, which lead to relapse. The adoption of immune checkpoint inhibitors (ICIs) in 2015, has offered exceptional survival benefits for patients without targetable alterations. Despite this notable progress, challenges remain, as not all patients respond favorably to ICIs, and resistance to therapy can develop over time. A crucial factor influencing clinical response to immunotherapy is the tumor microenvironment (TME). The TME is pivotal in orchestrating the interactions between neoplastic cells and the immune system, influencing tumor growth and treatment outcomes. In this review, we discuss how the understanding of this intricate relationship is crucial for the success of immunotherapy and survey the current state of immunotherapy intervention, with a focus on forthcoming and promising chimeric antigen receptor (CAR) T cell therapies in NSCLC. The TME sets major obstacles for CAR-T therapies, creating conditions that suppress the immune response, inducing T cell exhaustion. To enhance treatment efficacy, specific efforts associated with CAR-T cell therapy in NSCLC, should definitely focus TME-related immunosuppression and antigen escape mechanisms, by combining CAR-T cells with immune checkpoint blockades.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"16 ","pages":"1515748"},"PeriodicalIF":5.7,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11847692/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143491590","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}

{"title":"Bibliometric analysis of targeted immunotherapy for osteosarcoma-current knowledge, hotspots and future perspectives.","authors":"Yunxiang Hu, Rui Yang, Shuai Ni, Zefeng Song","doi":"10.3389/fimmu.2024.1485053","DOIUrl":"10.3389/fimmu.2024.1485053","url":null,"abstract":"<p><strong>Objective: </strong>The objective of this study is to conduct a bibliometric analysis on examining the current condition, areas of interest, and rising trends of immunotherapy for osteosarcoma (ITFOS), as well as its importance in associated research domains.</p><p><strong>Methods: </strong>An extensive collection of academic papers on the use of ITFOS was obtained from the Web of Science between January 1, 2000 and October 20, 2023. Then, using a variety of tools like HisCite, VOSviewer, CiteSpace, and the bibliometrix package, a bibliometric study was carried out. This study included the collection of information on country, institution, author, journal, and keywords.</p><p><strong>Results: </strong>A comprehensive analysis was undertaken on a total of 616 publications obtained from 247 journals, encompassing the contributions of 3725 authors affiliated with 831 institutes spanning across 43 countries/regions. Notably, China exhibited the highest quantity of published 277 (44.99%) articles on ITFOS. The most productive institution was Zhejiang University, with 26 (4.22%) publications. The author with the highest publication output was Tsukahara, Tomohide from Japan with 15 (2.44%) publications. The article with the most citation was \"DOI: 10.1200/JCO.2014.58.0225\". Frontiers in Immunology demonstrated the highest level of productivity, having published a total of 31 (5.03%) articles. The most frequently used were \"osteosarcoma,\" \"immunotherapy,\" and \"cancer,\". Meanwhile, \"sequencing\", \"prognostic signature\" and \"immune microenvironment\" have been identified as the research frontiers for the forthcoming years.</p><p><strong>Conclusion: </strong>This paper provides a thorough evaluation of current research trends and advancements in ITFOS. It includes relevant research findings and emphasizes collaborative efforts among authors, institutions, and countries.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"15 ","pages":"1485053"},"PeriodicalIF":5.7,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11847827/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143491729","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}

{"title":"A prognostic signature of Glutathione metabolism-associated long non-coding RNAs for lung adenocarcinoma with immune microenvironment insights.","authors":"Junxi Hu, Shuyu Tian, Qingwen Liu, Jiaqi Hou, Jun Wu, Xiaolin Wang, Yusheng Shu","doi":"10.3389/fimmu.2025.1477437","DOIUrl":"10.3389/fimmu.2025.1477437","url":null,"abstract":"<p><strong>Background: </strong>Glutathione (GSH) metabolism supports tumor redox balance and drug resistance, while long non-coding RNAs (lncRNAs) influence lung adenocarcinoma (LUAD) progression. This study developed a prognostic model using GSH-related lncRNAs to predict LUAD outcomes and assess tumor immunity.</p><p><strong>Methods: </strong>This study analyzed survival data from The Cancer Genome Atlas (TCGA) and identified GSH metabolism-related lncRNAs using Pearson correlation. A prognostic model was built with Cox and Least Absolute Shrinkage and Selection Operator (LASSO) methods and validated by Kaplan-Meier analysis, Receiver Operating Characteristic (ROC) curves, and Principal Component Analysis (PCA). Functional analysis revealed immune infiltration and drug sensitivity differences. Quantitative PCR and experimental studies confirmed the role of lnc-AL162632.3 in LUAD.</p><p><strong>Results: </strong>Our model included a total of nine lncRNAs, namely AL162632.3, AL360270.1, LINC00707, DEPDC1-AS1, GSEC, LINC01711, AL078590.2, AC026355.2, and AL096701.4. The model effectively forecasted patient survival, and the nomogram, incorporating additional clinical risk factors, satisfied clinical needs adequately. Patient stratification based on model scores revealed significant disparities in immune cell composition, functionality, and mutations between groups. Additionally, variations were noted in the IC50 values for key lung cancer medications such as Cisplatin, Docetaxel, and Paclitaxel. <i>In vitro</i> cell experiment results showed that AL162632.3 was markedly upregulated, while AC026355.2 tended to be downregulated across these cell lines. Ultimately, suppressing lnc-AL162632.3 markedly reduced the growth, mobility, and invasiveness of lung cancer cells.</p><p><strong>Conclusion: </strong>This study identified GSH metabolism-related lncRNAs as key prognostic factors in LUAD and developed a model for risk stratification. High-risk patients showed increased tumor mutation burden (TMB) and stemness, emphasizing the potential of personalized immunotherapy to improve survival outcomes.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"16 ","pages":"1477437"},"PeriodicalIF":5.7,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11847877/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143491730","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}

{"title":"Assessing hemorrhagic risks in combination therapy: implications of angiogenesis inhibitors and immune checkpoint inhibitors.","authors":"Yuhui Yang, Pingping Long, Ying Tuo, Xiaoxiao Wang","doi":"10.3389/fimmu.2025.1527570","DOIUrl":"10.3389/fimmu.2025.1527570","url":null,"abstract":"<p><strong>Objective: </strong>This study aims to evaluate the hemorrhage risk in solid tumor patients receiving angiogenesis inhibitors (AGIs), immune checkpoint inhibitors (ICIs), and their combination using the FDA Adverse Event Reporting System (FAERS) database.</p><p><strong>Methods: </strong>Data from Q1 2011 to Q4 2023 were extracted from the FAERS database for solid tumor patients treated with AGIs, ICIs, or their combination. A disproportionality analysis was conducted by calculating the reporting odds ratio (ROR) and corresponding 95% confidence interval (CI), as well as the Proportional Reporting Ratio (PRR), to identify potential safety signals. To assess whether the hemorrhage risk is higher with combination therapy compared to monotherapy, additive and multiplicative models were employed to evaluate the interactions between combination and single-agent treatments.</p><p><strong>Results: </strong>The combination of AGIs and ICIs significantly increased the risk of hemorrhagic adverse events, particularly tumor and pulmonary hemorrhage. Hemorrhagic events were common in females (50.97%) and older patients (aged 64+), frequently occurring within the first 30 days of treatment (38.11%). Gingival hemorrhage (ROR 3, PRR 418.9) and tumor hemorrhage (ROR 9.65, PRR 1893.36) were most common in the AGI group, while tumor hemorrhage (ROR 9.49, PRR 1350.78) and pulmonary hemorrhage (ROR 2.6, PRR 98.97) were prominent in the ICI group. In the combination group, esophageal variceal hemorrhage (ROR 40.72, PRR 2344.72) and tumor hemorrhage (ROR 19.31, PRR 1056.63) exhibited significantly increased risks Additive and multiplicative models indicated that the excess risk (RD_AB = 0.01025, P<0.001) and relative risk (RR_AB = 1.99277, P<0.001) of combination therapy were significantly higher than those of monotherapy, suggesting a positive interaction between the drugs that further increases the risk of hemorrhage.</p><p><strong>Conclusion: </strong>Our study demonstrates that the combination of AGIs and ICIs significantly raises the risk of hemorrhage, underscoring the urgent need for enhanced monitoring protocols in clinical practice to improve treatment efficacy and safety.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"16 ","pages":"1527570"},"PeriodicalIF":5.7,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11847817/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143491731","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}

{"title":"Case report: A severe myositis mimicking bulbar palsy after administration of immune checkpoint inhibitors.","authors":"Philippe Rochigneux, Alexandre Bertucci, Elika Loir, Alexia Mattei, Danielle Robert, Michael Dassa, Brice Chanez, Mikael Ebbo, Lea Gaigne, Anne Sophie Chretien, Giovanni Corazza, Nicolas Schleinitz","doi":"10.3389/fimmu.2025.1496427","DOIUrl":"10.3389/fimmu.2025.1496427","url":null,"abstract":"<p><strong>Objectives: </strong>Immune Checkpoint Inhibitors (ICI) are nowadays a cornerstone of anti-cancer treatments. However, the wide spectrum of immune-related adverse events (irAEs) represents a challenge in the oncological practice. Our objective is to document rare complications of ICI to help the community of onco-immunologists.</p><p><strong>Methods: </strong>We reported the case of a severe myositis mimicking bulbar palsy treated in our Medical Oncology Department together with Internal Medicine Department. We present the clinical work-up (neurological exam, capillaroscopy) and the diagnostic tests (myositis specific and associated antibodies, nerve conduction study, electromyography) leading to this diagnosis. We also discussed the elimination of differential diagnoses (notably with normal MRI and cerebrospinal fluid analysis) and finally the clinical management of this severe irAE.</p><p><strong>Results: </strong>A 57 years woman presented multiple sub-diaphragmatic adenopathies related with an advanced melanoma of unknown primary. She started a treatment with Ipilimumab (Ipi, anti CTLA-4) and Nivolumab (Nivo, anti PD-1) and presented at day 10 a grade IV myositis mimicking bulbar palsy with dysphonia, dysarthria and aphagia. In a multidisciplinary setting, she was treated with IV corticosteroids (methylprednisolone 1 mg/kg started at day 10, with a progressive decrease until 1 mg of prednisone in March 2024), IV immunoglobulins started at day 18 (1.5 g/kg in 2 days, administered monthly, with a progressive decrease and a cessation in June 2022), enteral nutrition, speech therapy and physical therapy, with noticeable improvement. After 4 years of follow-up, and only one infusion of Ipi/Nivo, the melanoma is still in complete response.</p><p><strong>Conclusion: </strong>We report an ICI-induced severe myositis mimicking bulbar palsy after the administration of Ipi/Nivo. The diagnosis and clinical care management of this rare complication requires a multi-disciplinary work-up.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"16 ","pages":"1496427"},"PeriodicalIF":5.7,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11847840/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143491735","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}

{"title":"Development and functional validation of a disulfidoptosis-related gene prognostic model for lung adenocarcinoma based on bioinformatics and experimental validation.","authors":"Tao Shen, Zhuming Lu, Sisi Yang, Dongxi Zhang, Yongwen Ke, Zhuowen Chen, Jinqiang Wu, Weidong Wu","doi":"10.3389/fimmu.2025.1540578","DOIUrl":"10.3389/fimmu.2025.1540578","url":null,"abstract":"<p><strong>Background: </strong>Disulfidoptosis is increasingly linked to cancer progression, yet its immunological impacts and prognostic value in lung adenocarcinoma (LUAD) remain poorly understood. This study aims to delineate the predictive significance of disulfidoptosis-related genes (DRGs) in LUAD, their potential as therapeutic targets, and their interaction with the tumor microenvironment.</p><p><strong>Methods: </strong>We analyzed the expression profiles of 23 DRGs and survival data, performing consensus clustering to identify molecular subtypes. Survival analysis and gene set variation analysis (GSVA) were used to explore cluster differences. Key DRGs were selected for Cox and LASSO regression to develop a prognostic model. Tensin4 (TNS4), a key gene in the model, was further evaluated through immunohistochemistry (IHC) in LUAD and normal tissues and gene knockdown experiments <i>in vitro</i>.</p><p><strong>Results: </strong>Two clusters were identified, with 225 differentially expressed genes. A six-gene signature was developed, which classified LUAD patients into high- and low-risk groups, showing significant survival differences. The risk score independently predicted LUAD prognosis and correlated with immunotherapy responses. IHC showed elevated TNS4 levels in LUAD tissues, while <i>in vitro</i> TNS4 knockdown reduced both cell proliferation and migration.</p><p><strong>Conclusion: </strong>This study highlights the role of DRGs in LUAD, with a validated gene signature offering new avenues for targeted therapies, potentially improving LUAD treatment outcomes.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"16 ","pages":"1540578"},"PeriodicalIF":5.7,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11847864/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143491595","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}

{"title":"Beyond the dichotomy: understanding the overlap between atopic dermatitis and psoriasis.","authors":"Mengmeng Li, Jiangyi Wang, Qingfeng Liu, Youqing Liu, Wenyao Mi, Wei Li, Jingyi Li","doi":"10.3389/fimmu.2025.1541776","DOIUrl":"10.3389/fimmu.2025.1541776","url":null,"abstract":"<p><p>Atopic dermatitis and psoriasis have traditionally been considered distinct inflammatory skin diseases with unique pathogenic mechanisms. However, accumulating evidence suggests significant overlap in their immunological pathways, metabolic features, and microbiome characteristics, challenging this conventional dichotomy. This review comprehensively examines the complex relationship between psoriasis and atopic dermatitis, with particular emphasis on their shared and distinct pathogenic mechanisms. We analyze the immunological networks, metabolic pathways, and microbial factors contributing to their development and progression. The review expands upon the disease spectrum hypothesis and discusses the nomenclature for conditions exhibiting features of both diseases. We critically evaluate the clinical and histopathological characteristics of concomitant psoriasis and atopic dermatitis, highlighting recent advances in molecular diagnostics for accurate disease differentiation. Importantly, we propose standardized diagnostic criteria for psoriasis dermatitis and examine current therapeutic strategies for managing overlapping conditions. Recent developments in targeted therapies and their implications for treatment selection are thoroughly discussed. By synthesizing current evidence and identifying knowledge gaps, this review provides insights into the complex interplay between psoriasis and atopic dermatitis, aiming to guide clinical decision-making and future research directions in this evolving field.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"16 ","pages":"1541776"},"PeriodicalIF":5.7,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11847814/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143491733","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}

{"title":"CD32B1, a versatile non-signaling antibody-binding scaffold for enhanced T cell adhesion to tumor stromal cognate antigens.","authors":"Sara W Feigelson, Tali Dadosh, Nehora Levi, Anita Sapoznikov, Hadas Weinstein-Marom, Dayana Blokon-Kogan, Yahel Avraham, Tamar Unger, Gideon Gross, Rony Dahan, Ronen Alon","doi":"10.3389/fimmu.2025.1398757","DOIUrl":"10.3389/fimmu.2025.1398757","url":null,"abstract":"<p><p>Targeting cytotoxic T lymphocytes (CTLs), as chimeric antigen T cells (CAR-T), T cell receptor-engineered (TCR)-T cells or adoptive cell transfer of tumor infiltrating T cells (TILs) to solid tumors is a major therapeutic challenge. We describe a new strategy to confer these lymphocytes with <i>de novo</i> adhesiveness to surface proteins enriched in the tumor microenvironment. This approach is based on decorating CTLs with monoclonal antibodies (mAbs) specific to any surface protein of interest within the stroma and the extracelullar matrix of solid tumors. For efficient mAb decoration, we have introduced a mAb binding Fc receptor (FcR) scaffold, FcγRIIB1 (CD32B1), which we found to be enriched on B lymphocyte microvilli (MV). This isoform contains an inhibitory ITIM motif within a cytoplasmic tail anchored to the cortical cytoskeleton. We thus generated a non-signaling CD32B1 mutant lacking the ITIM motif (termed ITIM-less CD32B1, or ILCD32B1) and successfully expressed it in human T cells which normally do not express this FcR. The ILCD32B1 expressing lymphocytes bound multiple IgG1 mAbs whose Fc domain was engineered with a 5-residue substitution to reach a nM range of Fc-FcγCR dissociation constants. The mAb decorated ILCD32B1 expressing T cells could readily adhere to a surface-bound cognate antigen. To broaden the utility of this scaffold, we have also generated a new fusion protein in which the entire Fc binding domain was truncated (tILCD32B1) and replaced with a monomeric streptavidin variant, mSA2, via a CD8 hinge. The molecule, termed mSA2-CD8h-tILCD32B1, was also successfully expressed in T cells, readily and stably bound biotinylated IgG mAbs <i>in vitro</i> and once decorated with the biotin labeled mAbs, conferred the T cells with high adhesiveness to multiple surface-coated antigens. mSA2-CD8h-tILCD32B1 expressing human T cells decorated ex vivo with a biotin-labeled mAb retained the antibody for hours after accumulation inside breast tumors implanted in immunodeficient recipient mice. Our results collectively suggest that a non-signaling CD32B1 can be used as a versatile scaffold for mAb decoration of T cells. Our mAb decoration approach can confer new cell adhesive reactivities to improve tumor CTL (CAR-T and TIL) accumulation and retention inside solid tumors.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"16 ","pages":"1398757"},"PeriodicalIF":5.7,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11847833/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143491736","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}