Frontiers in Immunology最新文献

{"title":"Effects of isolated, confined and extreme environments on parameters of the immune system - a systematic review.","authors":"Bea Klos, Alina Kaul, Emily Straube, Verena Steinhauser, Celina Gödel, Franziska Schäfer, Claude Lambert, Paul Enck, Isabelle Mack","doi":"10.3389/fimmu.2025.1532103","DOIUrl":"https://doi.org/10.3389/fimmu.2025.1532103","url":null,"abstract":"<p><strong>Background: </strong>The immune system is a crucial part of the body's defense against infection and disease. However, individuals in antigen-limited environments face unique challenges that can weaken their immune systems. This systematic review aimed to investigate the impact of an exposure to an isolated, confined and extreme (ICE) environment with limited antigen diversity on human immune parameters.</p><p><strong>Methods: </strong>A systematic literature search was conducted using PubMed, Web of Science and Cochrane Library to identify relevant studies on immune system parameters in ICE environments. The studies were grouped by ICE type (space missions, microgravity simulations like bed rest studies, space simulation units like MARS500, and Antarctic research stations) to allow for clearer comparison and analysis of immune outcomes.</p><p><strong>Results: </strong>Analysis of 140 studies revealed considerable heterogeneity in study designs and outcomes, reflecting the complexity of immune responses across ICE environments. Nevertheless, immune dysregulation was consistently observed across environments. Space missions and Antarctic stations, in particular, showed pronounced immune changes, likely due to low antigen diversity and extreme conditions, with higher rates of infections and allergic responses suggesting increased vulnerability. Space simulation units exhibited immune changes similar to those in actual space missions, while gravity simulation studies, which focus on fluid shifts and bone loss, showed fewer immune alterations. Across environments, most immunological measures returned to baseline after isolation, indicating resilience and the potential for recovery upon re-exposure to diverse antigens.</p><p><strong>Conclusion: </strong>Reduced antigen diversity in ICE environments disrupts immune function, with effects often compounded by extreme conditions. Although immune resilience and recovery post-isolation are promising, the heterogeneity in current studies highlights the need for targeted research to identify specific immune vulnerabilities and to develop countermeasures. Such measures could reduce immune-related health risks for individuals in isolated settings, including astronauts, polar researchers, and vulnerable populations on Earth, such as the elderly or immunocompromised, thereby enhancing resilience in confined environments.</p><p><strong>Systematic review registration: </strong>https://www.crd.york.ac.uk/prospero/, identifier CRD42023476132.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"16 ","pages":"1532103"},"PeriodicalIF":5.7,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11975566/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143811087","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":"<i>Plasmodium falciparum</i> reticulocyte-binding homologues are targets of human inhibitory antibodies and play a role in immune evasion.","authors":"Linda Reiling, Kristina E M Persson, Fiona J McCallum, Nimmo Gicheru, Samson M Kinyanjui, Chetan E Chitnis, Freya J I Fowkes, Kevin Marsh, James G Beeson","doi":"10.3389/fimmu.2025.1532451","DOIUrl":"https://doi.org/10.3389/fimmu.2025.1532451","url":null,"abstract":"<p><strong>Introduction: </strong>Antibodies targeting the blood-stage of <i>Plasmodium falciparum</i> play a critical role in naturally acquired immunity to malaria by limiting blood-stage parasitemia. One mode of action of antibodies is the direct inhibition of merozoite invasion of erythrocytes through targeting invasion ligands. However, evasion of inhibitory antibodies may be mediated in <i>P. falciparum</i> by switching between various ligand-mediated merozoite invasion pathways. Here, we investigated the potential roles of invasion ligands PfRH1, PfRH2a and PfRH2b in immune evasion through phenotypic variation, and their importance as targets of human invasion-inhibitory antibodies.</p><p><strong>Methods: </strong>Serum samples from malaria-exposed children and adults in Kenya were examined for their ability to inhibit <i>P. falciparum</i> invasion, using parasites with disrupted pfrh1, pfrh2a or pfrh2b genes.</p><p><strong>Results and discussion: </strong>The loss of PfRH1 and PfRH2b substantially impacted on susceptibility to inhibitory antibodies, suggesting that variation in the use of these ligands contributes to immune evasion. The effect was less prominent with loss of PfRH2a. Differential inhibition of the knockout and parental lines points to PfRH1 and PfRH2b as targets of acquired growth inhibitory antibodies whereas PfRH2a appeared to be a minor target. There was limited relatedness of the inhibitory responses between different isolates or compared to parasites with deletions of erythrocyte-binding antigens. This further suggests that there is a substantial amount of antigenic diversity in invasion pathways to facilitate immune evasion. These findings provide evidence that PfRH1 and PfRH2b are significant targets of inhibitory antibodies and variation in their expression may facilitate immune evasion. Targeting of multiple invasion ligands in vaccine design is likely to be required to achieve potent inhibitory antibodies and protective efficacy against malaria.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"16 ","pages":"1532451"},"PeriodicalIF":5.7,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11975925/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143811071","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":"Immune cells differentiation in osteoarthritic cartilage damage: friends or foes?","authors":"Mingxiang Liu, Chaoqun Wu, Chaofan Wu, Zulong Zhou, Run Fang, Chenfeng Liu, Rende Ning","doi":"10.3389/fimmu.2025.1545284","DOIUrl":"https://doi.org/10.3389/fimmu.2025.1545284","url":null,"abstract":"<p><p>Osteoarthritis (OA) is a chronic disease primarily characterized by degenerative changes in articular cartilage and synovitis, for which there are currently no targeted or curative therapies available in clinical practice. In recent years, the in-depth analysis of OA using single-cell sequencing and immunomics technologies has revealed the presence of multiple immune cell subsets, as well as different differentiation states within the same subset, in OA. Through immune-immune and immune-joint tissue interactions, these cells collectively promote or inhibit the progression of arthritis. This complex immune network, where \"friends and foes coexist,\" has made targeted therapeutic strategies aimed at directly eliminating immune cells challenging, highlighting the urgent need for a detailed review of the composition, distribution, functional heterogeneity, therapeutic potential, and potential risks of immune subsets within the joint. Additionally, the similarities and differences between OA and rheumatoid arthritis (RA) in terms of diagnosis and immunotherapy need to be precisely understood, in order to draw lessons from or reject RA-based immunotherapies. To this end, this review summarizes the major triggers of inflammation in OA, the differentiation characteristics of key immune cell subsets, and compares the similarities and differences between OA and RA in diagnosis and treatment. It also outlines the current immunomodulatory strategies for OA and their limitations. Furthermore, we provide a detailed and focused discussion on immune cells that act as \"friends or foes\" in arthritis, covering the M1/M2 polarization of macrophages, functional heterogeneity of neutrophils, unique roles of dendritic cells at different maturation states, the balance between pro-inflammatory T cells and regulatory T cells (Tregs), and the diverse functions of B cells, plasma cells, and regulatory B cells (Bregs) in OA. By interpreting the roles of these immune cells, this review clarifies the dynamic changes and interactions of immune cells in OA joints, providing a theoretical foundation for more precise targeted interventions in future clinical practice.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"16 ","pages":"1545284"},"PeriodicalIF":5.7,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11975574/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143811089","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":"The conflicting role highlights the complexity of GSDMs in cancer.","authors":"Sijia He, Qian Huang, Jin Cheng","doi":"10.3389/fimmu.2025.1531695","DOIUrl":"https://doi.org/10.3389/fimmu.2025.1531695","url":null,"abstract":"<p><p>Gasdermins (GSDMs) are an important family of proteins that have received extensive attention in tumor research in recent years. They directly induce tumor cell death by mediating pyroptosis and also regulate the recognition and clearance of tumor cells by the immune system by affecting the microenvironment. Therefore, it is of great significance to investigate the role of GSDMs in tumor development and tumor microenvironment. It can not only reveal new mechanisms of cancer development, but also provide theoretical basis for the development of novel anti-tumor therapeutic strategies. This literature review aims to systematically summarize the dual roles of GSDMs in tumor development and their interactions with the tumor microenvironment, and to focus on the importance of GSDM-mediated pyroptosis in anti-cancer therapy, with a view to providing guidance for future research directions.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"16 ","pages":"1531695"},"PeriodicalIF":5.7,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11975587/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143811107","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":"Modulation of pulmonary immune functions by the <i>Pseudomonas aeruginosa</i> secondary metabolite pyocyanin.","authors":"Shi Qian Lew, Sook Yin Chong, Gee W Lau","doi":"10.3389/fimmu.2025.1550724","DOIUrl":"10.3389/fimmu.2025.1550724","url":null,"abstract":"<p><p><i>Pseudomonas aeruginosa</i> is a prevalent opportunistic Gram-negative bacterial pathogen. One of its key virulence factors is pyocyanin, a redox-active phenazine secondary metabolite that plays a crucial role in the establishment and persistence of chronic infections. This review provides a synopsis of the mechanisms through which pyocyanin exacerbates pulmonary infections. Pyocyanin induces oxidative stress by generating reactive oxygen and nitrogen species which disrupt essential defense mechanisms in respiratory epithelium. Pyocyanin increases airway barrier permeability and facilitates bacterial invasion. Pyocyanin also impairs mucociliary clearance by damaging ciliary function, resulting in mucus accumulation and airway obstruction. Furthermore, it modulates immune responses by promoting the production of pro-inflammatory cytokines, accelerating neutrophil apoptosis, and inducing excessive neutrophil extracellular trap formation, which exacerbates lung tissue damage. Additionally, pyocyanin disrupts macrophage phagocytic function, hindering the clearance of apoptotic cells and perpetuating inflammation. It also triggers mucus hypersecretion by inactivating the transcription factor FOXA2 and enhancing the IL-4/IL-13-STAT6 and EGFR-AKT/ERK1/2 signaling pathways, leading to goblet cell metaplasia and increased mucin production. Insights into the role of pyocyanin in <i>P. aeruginosa</i> infections may reveal potential therapeutic strategies to alleviate the severity of infections in chronic respiratory diseases including cystic fibrosis (CF) and chronic obstructive pulmonary disease (COPD).</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"16 ","pages":"1550724"},"PeriodicalIF":5.7,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11973339/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143802997","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 bivalent mRNA vaccine against RSV infection in rodent models.","authors":"Juan Liu, Hanqing Zhao, Wenhao Wang, Binbin Yang, Naifang Zhang, Yu Zhang, Jie Qian, Qiaofang Ma, Yankun Lu, Huafeng Han, Yongsheng Yang","doi":"10.3389/fimmu.2025.1542592","DOIUrl":"10.3389/fimmu.2025.1542592","url":null,"abstract":"<p><p>Because of the higher conservation of RSV Fusion (F) protein than the glycoprotein (G) across RSV strains and serotypes, the majority of vaccine candidates targets to viral fusion protein (F) rather than glycoprotein to elicit a broader range of protective neutralizing antibodies from infection. In this study, we screened two chemically modified mRNA vaccines expressing RSV prefusion stabilized protein (preF) targeting RSV A2 and B subtypes. After immunization, the antigen-specific binding antibody, neutralizing antibody, and T cell-mediated immune response were evaluated. After challenge with live RSV A2 virus in cotton rats, the protection and safety of vaccine was further evaluated. The results showed that the mRNA vaccine candidates elicited robust antigen-specific binding antibody, neutralizing antibody responses and Th1-biased T-cell responses in both mice and cotton rats. Moreover, cotton rats vaccinated with mRNA vaccine, lung pathology and lung infectious viral loads were significantly reduced, and no vaccine enhanced respiratory disease (VERD) happened. These results collectively demonstrated that mRNA-based vaccine induced strong humoral and cellular immunity, provided outstanding protection against both RSV A2 and RSV B subtypes in rodent animals as well. Our data demonstrated that these mRNA vaccines should be further evaluated in clinical trials.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"16 ","pages":"1542592"},"PeriodicalIF":5.7,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11974254/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143803021","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":"Macrophage activation syndrome successfully treated with eculizumab and emapalumab: a case report.","authors":"Paola Faggioli, Marianna Galeazzi, Carlotta Ferrari, Francesca Capelli, Chiara Marchesi, Lucia Marchionni, Laura Castelnovo, Antonio Tamburello, Eugenio Capparelli, Cristina Campidelli, Antonino Mazzone","doi":"10.3389/fimmu.2025.1555415","DOIUrl":"10.3389/fimmu.2025.1555415","url":null,"abstract":"<p><p>Hemophagocytic lymphohistiocytosis (HLH) is a hyperinflammatory syndrome, often referred to as macrophage activation syndrome (MAS) in the context of autoimmune disease-induced forms. We report the case of a 41-year-old woman with a previous diagnosis of Crohn's disease complicated by dermatomyositis, who was admitted in our hospital for the acute onset of fever, pancytopenia, and disseminated intravascular coagulation (DIC). The laboratory findings documented hyperferritinemia, hypertransaminasemia, increased lactate-dehydrogenase (LDH), hypertriglyceridemia, and elevation of inflammatory indices, along with complement consumption. MAS was confirmed by examination of the bone marrow. Consequently, the patient was treated with high doses of glucocorticoids, subcutaneous anakinra, and intravenous immunoglobulin (IVIg). Due to the persistence of signs of thrombotic microangiopathy, we started therapy with eculizumab which stabilized the patient without improvement, so we added emapalumab, resulting in clinical improvement and normalization of blood tests.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"16 ","pages":"1555415"},"PeriodicalIF":5.7,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11973329/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143803044","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":"CMTM3 regulates vascular endothelial cell dysfunction by influencing pulmonary vascular endothelial permeability and inflammation in ARDS.","authors":"Ziyan Xiao, Gang Zhou, Haiyan Xue, Lihe Chen, Xiujuan Zhao, Shu Li, Chun Fu, Zhengzhou Wang, Fengxue Zhu","doi":"10.3389/fimmu.2025.1544610","DOIUrl":"10.3389/fimmu.2025.1544610","url":null,"abstract":"<p><strong>Introduction: </strong>CMTM3 is a member of the human chemokine-like factor superfamily. The mechanistic role of CMTM3 in acute respiratory distress syndrome (ARDS) is not known. This study investigated the role of CMTM3 in the progression of ARDS and its impact on the function of vascular endothelial cells.</p><p><strong>Methods: </strong>ARDS modeling in human umbilical vascular endothelial cells (HUVECs) was performed by treating with lipopolysaccharide (LPS) or hypoxia/reoxygenation. We assessed CMTM3 expression levels in the LPS- and hypoxia/reoxygenation-stimulated HUVEC cells. Furthermore, we assessed the role of CMTM3 in the permeability function and inflammatory response of the vascular endothelial cells under ARDS conditions using HUVEC cells with CMTM3 overexpression(adCMTM3) or knockdown(shCMTM3). Concurrently, we generated CMTM3 knockout (CMTM3ko) mice and evaluated the differences in pulmonary vascular permeability, inflammatory lung injury, and survival rates between the CMTM3ko-ARDS and WT-ARDS model mice.</p><p><strong>Results: </strong>HUVECs stimulated with LPS and hypoxia/reoxygenation showed significantly higher CMTM3 expression compared to the control group (p<0.05). Compared with the adsham-HUVECs, adCMTM3-HUVECs stimulated with LPS and hypoxia/reoxygenation demonstrated significantly higher cellular permeability (p<0.05) as well as IL-6 and TNF-α expression levels (p<0.05). Conversely, shCMTM3-HUVECs stimulated with LPS and hypoxia/reoxygenation showed significantly reduced cellular permeability as well as IL-6 and TNF-α expression levels (p<0.05). In vivo ARDS modeling experiments demonstrated that CMTM3-knockout ARDS mice exhibited significantly higher survival rates (p=0.0194) as well as significantly reduced lung injury and pulmonary vascular permeability (p<0.05) compared to the wild-type ARDS mice.</p><p><strong>Discussion: </strong>These findings demonstrated that CMTM3 played a critical role in the development of ARDS by influencing permeability of the pulmonary vascular endothelial cells and lung inflammation. Therefore, CMTM3 is a potential therapeutic target in ARDS.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"16 ","pages":"1544610"},"PeriodicalIF":5.7,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11973065/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143802962","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":"Predicting reverse-bound peptide conformations in MHC Class II with PANDORA.","authors":"Daniel T Rademaker, Farzaneh M Parizi, Marieke van Vreeswijk, Sanna Eerden, Dario F Marzella, Li C Xue","doi":"10.3389/fimmu.2025.1525576","DOIUrl":"10.3389/fimmu.2025.1525576","url":null,"abstract":"<p><p>Recent discoveries have transformed our understanding of peptide binding in Major Histocompatibility Complex (MHC) molecules, showing that peptides, for some MHC class II alleles, can bind in a reverse orientation (C-terminus to N-terminus) and can still effectively activate CD4+ T cells. These finding challenges established concepts of immune recognition and suggests new pathways for therapeutic intervention, such as vaccine design. We present an updated version of PANDORA, which, to the best of our knowledge, is the first tool capable of modeling reversed-bound peptides. Modeling these peptides presents a unique challenge due to the limited structural data available for these orientations in existing databases. PANDORA has overcome this challenge through integrative modeling using algorithmically reversed peptides as templates. We have validated the new PANDORA feature through two targeted experiments, achieving an average backbone binding-core L-RMSD value of 0.63 Å. Notably, it maintained low RMSD values even when using templates from different alleles and peptide sequences. Our results suggest that PANDORA will be an invaluable resource for the immunology community, aiding in the development of targeted immunotherapies and vaccine design.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"16 ","pages":"1525576"},"PeriodicalIF":5.7,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11973093/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143803015","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 tumor-infiltrating B lymphocytes -related index based on machine-learning predicts prognosis and immunotherapy response in lung adenocarcinoma.","authors":"Jiale Fang, Siyuan Yu, Wei Wang, Cheng Liu, Xiaojia Lv, Jiaqi Jin, Xiaomin Han, Fang Zhou, Yukun Wang","doi":"10.3389/fimmu.2025.1524120","DOIUrl":"10.3389/fimmu.2025.1524120","url":null,"abstract":"<p><strong>Introduction: </strong>Tumor-infiltrating B lymphocytes (TILBs) play a pivotal role in shaping the immune microenvironment of tumors (TIME) and in the progression of lung adenocarcinoma (LUAD). However, there remains a scarcity of research that has thoroughly and systematically delineated the characteristics of TILBs in LUAD.</p><p><strong>Method: </strong>The research employed single-cell RNA sequencing from the GSE117570 dataset to identify markers linked to TILBs. A comprehensive machine learning approach, utilizing ten distinct algorithms, facilitated the creation of a TILB-related index (BRI) across the TCGA, GSE31210, and GSE72094 datasets. We used multiple algorithms to evaluate the relationships between BRI and TIME, as well as immune therapy-related biomarkers. Additionally, we assessed the role of BRI in predicting immune therapy response in two datasets, GSE91061 and GSE126044.</p><p><strong>Result: </strong>BRI functioned as an independent risk determinant in LUAD, demonstrating a robust and reliable capacity to predict overall survival rates. We observed significant differences in the scores of B cells, M2 macrophages, NK cells, and regulatory T cells between the high and low BRI score groups. Notably, BRI was found to inversely correlate with cytotoxic CD8+ T-cell infiltration (r = -0.43, p < 0.001) and positively correlate with regulatory T cells (r = 0.31, p = 0.008). We also found that patients with lower BRI were more likely to respond to immunotherapy and were associated with reduced IC50 values for standard chemotherapy and targeted therapy drugs, in contrast to higher BRI. Additionally, the BRI-based survival prediction nomogram demonstrated significant promise for clinical application in predicting the 1-, 3-, and 5-year overall survival rates among LUAD patients.</p><p><strong>Discussion: </strong>Our study developed a BRI model using ten different algorithms and 101 algorithm combinations. The BRI could be a valuable tool for risk stratification, prognosis, and selection of treatment approaches.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"16 ","pages":"1524120"},"PeriodicalIF":5.7,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11973313/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143803035","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}