Frontiers in Immunology最新文献

{"title":"Comprehensive immunoinformatics and bioinformatics strategies for designing a multi-epitope based vaccine targeting structural proteins of Nipah virus.","authors":"Shivangi Sharma, Pragya D Yadav, Sarah Cherian","doi":"10.3389/fimmu.2025.1535322","DOIUrl":"10.3389/fimmu.2025.1535322","url":null,"abstract":"<p><strong>Background: </strong>Nipah virus (NiV) is characterized by recurring outbreaks and causes severe neurological impact, leading to increased mortality rates. Despite the severity of the disease, there is no proven post-exposure treatment available, emphasizing the critical need for the development of an effective vaccine.</p><p><strong>Objective: </strong>This study was aimed at designing a multi-epitope based vaccine candidate based on an in-silico approach.</p><p><strong>Methods: </strong>NiV's Structural proteins were screened for B and T-cell epitopes, assessing characteristics like antigenicity, immunogenicity, allergenicity, and toxicity. Two vaccine constructs (NiV_1 & 2) were designed using different adjuvants (Cholera toxin and Beta-defensin 3) and linkers and their predicted 3D structures were evaluated for interaction with Toll-Like Receptor TLR-3 using docking and molecular dynamics (MD) simulation studies. Finally, The potential expression of the vaccine construct in Escherichia coli (E. coli.) was verified by cloning it into the PET28a (+) vector and immune simulations were undertaken.</p><p><strong>Results: </strong>The study identified 30 conserved, antigenic, immunogenic, non-allergenic, and non-toxic epitopes with a broad population coverage. Based on the stability of vaccine construct in MD simulations results, NiV_1 was considered for further analysis. <i>In-silico</i> immune simulations of NiV_1 indicated a substantial immunogenic response. Moreover, codon optimization and in-silico cloning validated the expressions of designed vaccine construct NiV_1 in E. coli.</p><p><strong>Conclusion: </strong>The findings indicate that the NiV_1 vaccine construct has the potential to elicit both cellular and humoral immune responses. Additional <i>in vitro</i> and <i>in vivo</i> investigations are required to validate the computational observations.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"16 ","pages":"1535322"},"PeriodicalIF":5.7,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12106399/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144157848","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":"Corrigendum: Regulation of the immune microenvironment by SUMO in diabetes mellitus.","authors":"Yuting Zhuo, Shangui Fu, Yue Qiu","doi":"10.3389/fimmu.2025.1621597","DOIUrl":"https://doi.org/10.3389/fimmu.2025.1621597","url":null,"abstract":"<p><p>[This corrects the article DOI: 10.3389/fimmu.2025.1506500.].</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"16 ","pages":"1621597"},"PeriodicalIF":5.7,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12108100/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144157936","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":"Efficacy and safety of CD19 combined with CD22 or CD20 chimeric antigen receptor T-cell therapy for hematological malignancies.","authors":"Xiaoshuang Yuan, Feiqing Wang, Peng Zhao, Bo Yang, Xu Yang, Ting Tian, Bingbing Li, Guangyang Liu, Sanbin Wang, Dongxin Tang, Zhixu He, Yanju Li, Yang Liu","doi":"10.3389/fimmu.2025.1577360","DOIUrl":"10.3389/fimmu.2025.1577360","url":null,"abstract":"<p><strong>Background: </strong>CD19 combined with CD22 or CD20 therapy is a promising immunotherapy approach for the treatment of hematological malignancies. Dual-targeted CD19/CD22 CAR T and CD19/CD22 CAR T-cell therapy are currently being evaluated in clinical trials, and the extent of improvement using CD19 in combination with dual-targeted therapy has not yet been determined. To compare the differences between the two in the treatment of hematological tumors, this study summarized the available evidence. To evaluate and compare the efficacy and safety of CD19-combined CD22 and CD19-combined CD20 CAR T-cell therapy.</p><p><strong>Methods: </strong>Data from 13 clinical studies that included 628 patients with hematological malignancies were extracted and analyzed based on a set of inclusion and exclusion criteria. The primary efficacy outcomes were overall response rate (ORR), complete response (CR) rate, partial response (PR) rate, overall survival (OS) rate and minimal residual disease (MRD)-negative response rate. The safety outcomes were cytokine release syndrome (CRS) rate and immune effector cell-associated neurotoxicity syndrome (ICANS) rate.</p><p><strong>Results: </strong>For CD19 combined with CD22 CAR T-cell therapy, the ORR was 83.7%; CR, 78.0%; PR, 20.7%, OS, 78.7%; MRD-negative response rate, 82.3%; incidence of CRS, 58.2%; ICANS, 7.7%. For CD19 combined with CD20 CAR T-cell therapy, the ORR was 80.3%; CR, 68.2%; PR, 10.9%; OS, 76.8%; incidence of CRS, 54.5%; ICANS, 21%. Subgroup analysis indicated that the PR of CD19 combined with CD22 was significantly greater than that of CD19 combined with CD20, and the incidence of ICANS was significantly lower with the CD19+CD22 CAR-T combination.</p><p><strong>Conclusion: </strong>The data from this study suggest that CD19 combined with CD22 CAR T-cell therapy had a higher partial response rate in the treatment of hematologic malignancies and higher safety profile in the occurrence of ICANS than CD19 combined with CD20. These data provide an important clinical basis for the development of new therapeutic targets and the construction of therapeutic methods for the treatment of hematologic malignancies, and broaden our understanding of CD19 dual-targeted CAR T therapy.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"16 ","pages":"1577360"},"PeriodicalIF":5.7,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12106392/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144157950","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":"Tracing the history of clinical practice of liquid biopsy: a bibliometric analysis.","authors":"Shuo Zhang, Hongwei Zhao, Kangchun Wang, Lijie Li, Qi Pan, Meitong Lu, Xing Zhang","doi":"10.3389/fimmu.2025.1574736","DOIUrl":"10.3389/fimmu.2025.1574736","url":null,"abstract":"<p><strong>Introduction: </strong>Liquid biopsy holds great promise in clinical diagnosis, treatment, and prognostic monitoring. This study reveals the development of liquid biopsy in clinical practice through a comprehensive bibliometric analysis.</p><p><strong>Methods: </strong>A total of 40 years of research literature in this field was included from the Web of Science Core Collection (WoSCC), analyzing the evolving research trends of liquid biopsy in clinical practice. We constructed co-occurrence networks for countries, institutions, authors, and keywords, integrating citation analysis and journal impact metrics to provide a comprehensive view of the research landscape in the field of liquid biopsy.</p><p><strong>Results: </strong>The results show a significant growth trend in the clinical practice of liquid biopsy, with China and the United States being the leading contributors. Institutions such as Harvard University and the University of California system play a central role in the global collaboration network. Cancers has become the primary publication outlet for the field, while highly cited journals like Clinical Cancer Research play a crucial role in advancing its development. Keyword analysis reveals that research has progressively expanded into clinical applications, personalized treatment, and prognostic evaluation.</p><p><strong>Discussion: </strong>Overall, as technology and applications continue to mature, liquid biopsy is expected to play an even greater role in the early diagnosis, treatment evaluation, and personalized treatment of cancer and other diseases.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"16 ","pages":"1574736"},"PeriodicalIF":5.7,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12105997/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144157980","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":"SARM1: a key multifaceted component in immunoregulation, inflammation and neurodegeneration.","authors":"Samuel Dos Santos Oliveira, João Vinícius Honório da Silva, Raquel de Souza Vieira, Luís Felipe Serra Moreira, Pedro Henrique Araújo Bandeira, Beatriz Leocata Ramos, Marco Antônio Ataíde Silva, Niels Olsen Saraiva Câmara","doi":"10.3389/fimmu.2025.1521364","DOIUrl":"10.3389/fimmu.2025.1521364","url":null,"abstract":"<p><p>The downstream signaling pathways of TLR activation involve a family of adaptor proteins, including MYD88, TIRAP, TRIF, TRAM, and SARM1. The first four proteins stimulate inflammatory and antiviral responses, playing crucial roles in innate immunity against various pathogens. In contrast, SARM1 promotes immunity to microorganisms in invertebrate animals independently of TLRs, and negatively regulates inflammatory responses in metazoan organisms. SARM1 inhibits TRIF, reduces the activation of various inflammasomes, and induces mitochondrial damage and cell death to eliminate hyperactivated cells. This regulation is essential to ensure timely control of immune responses and to prevent excessive inflammation. Recently, it was discovered that SARM1 can hydrolyze NAD, a critical component of cellular metabolism. The reduction of NAD levels by SARM1 is linked to the progression of Wallerian degeneration following neuronal injury and may also play a role in the immunoregulation of lymphoid and myeloid cells. Since SARM1 can be pharmacologically modulated, it presents promising opportunities for developing treatments for inflammatory and neurodegenerative diseases.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"16 ","pages":"1521364"},"PeriodicalIF":5.7,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12106052/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144157972","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":"HDAC6 inhibition by ITF3756 modulates PD-L1 expression and monocyte phenotype: insights for a promising immune checkpoint blockade co-treatment therapy.","authors":"Valeria Spadotto, Chiara Ripamonti, Andrea Ghiroldi, Elisabetta Galbiati, Pietro Pozzi, Roberta Noberini, Tiziana Bonaldi, Christian Steinkühler, Gianluca Fossati","doi":"10.3389/fimmu.2025.1546939","DOIUrl":"10.3389/fimmu.2025.1546939","url":null,"abstract":"<p><strong>Introduction: </strong>Tumor immunotherapy has revolutionized cancer treatment, particularly through the use of immune checkpoint inhibitors targeting the PD-L1/PD-1 axis. While PD-L1 expression on tumor cells is an established predictive biomarker for therapeutic response, emerging evidence highlights the importance of PD-L1 expression on myeloid cells, both in the periphery and within the tumor microenvironment (TME). This study explores the immunomodulatory effects of the selective HDAC6 inhibitor ITF3756 on monocytes and dendritic cells (DCs).</p><p><strong>Methods: </strong>Monocytes were stimulated with the pro-inflammatory cytokine TNF-α and treated with ITF3756. PD-L1 and CD40 expression levels were assessed by flow cytometry. Transcriptomic and proteomic analyses were performed to characterize changes in gene and protein expression profiles. T cell proliferation was evaluated in co-culture assays. Additionally, the impact of ITF3756 was assessed in an in vivo murine model of colon cancer.</p><p><strong>Results: </strong>ITF3756 effectively downregulated PD-L1 expression in TNF-α-activated monocytes and enhanced their costimulatory capacity by increasing CD40 expression. Transcriptomic and proteomic analyses revealed that ITF3756 counteracted TNF-α pathway activation and downregulated multiple inhibitory immune checkpoint molecules, promoting a less immunosuppressive phenotype. In co-culture assays, ITF3756-treated monocytes and DCs significantly enhanced T cell proliferation. In vivo, ITF3756 treatment led to reduced tumor growth in a colon cancer model.</p><p><strong>Discussion: </strong>These findings demonstrate that selective HDAC6 inhibition by ITF3756 modulates myeloid cell functionality by diminishing inhibitory signals and promoting T cell activation. Thus, ITF3756 represents a promising immunomodulatory agent that could enhance the efficacy of immune checkpoint blockade in cancer immunotherapy.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"16 ","pages":"1546939"},"PeriodicalIF":5.7,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12106391/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144157967","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":"Immunoinformatic-driven design and evaluation of multi-epitope mRNA vaccine targeting HIV-1 gp120.","authors":"Muhammad Zeeshan Ahmed, Tazeen Rao, Zeeshan Mutahir, Sarfraz Ahmed, Najeeb Ullah, Suvash Chandra Ojha","doi":"10.3389/fimmu.2025.1480025","DOIUrl":"10.3389/fimmu.2025.1480025","url":null,"abstract":"<p><p>HIV (human immunodeficiency virus) presents a global health crisis, causing significant AIDS-related deaths and over one million new infections annually. The curbing of HIV is an intricate and continuously evolving domain, marked by numerous challenges, including drug resistance and the absence of a significant cure or vaccine because of its mutating ability and diverse antigens in its envelope, prompting research for functional cures and long-term remission strategies. The endeavor to devise an HIV vaccine capable of eliciting robust and broadly cross-reactive humoral and cellular immune responses is a formidable undertaking, primarily due to the pronounced genetic heterogeneity of HIV-1, the variances observed in virus subtypes (clades) across distinct geographic regions, and the polymorphic nature of human leukocyte antigens (HLA). The viral envelope protein (gp120) selectively interacts with CD4 and chemokine receptors on the surface of target cells. It serves as the key initiator in the intricate viral entry into host cells, rendering it a compelling candidate for vaccine development. This study used bioinformatic tools to design a safe, hypoallergenic, and non-toxic mRNA HIV-1 vaccine by assembling immunogenic B- and T-cell epitopes from the gp120 protein. We identified antigenic, non-toxic, and non-allergic B-cell epitopes (IEPLGIAPTRAKRRVVER) and T-cell epitopes (QQKVHALFY, ITIGPGQVF, WQGVGQAMY, APTRAKRRV, KQQKVHALFYRLDIV, QQKVHALFYRLDIVQ, QKVHALFYRLDIVQI, SLAEEEIIIRSENLT, and IRSENLTNNVKTIIV). For designing the mRNA vaccine against HIV-1 gp120, we assembled the epitopes with 5' m7G cap, 5' UTR (untranslated region), Kozak sequence, signal peptide (tPA), RpfE (resuscitation-promoting factor E) adjuvant at N-terminal and MITD (MHC class I trafficking domain) adjuvant, stop codon, 3' UTR, and 120-nucleotide long poly(A) tail at the C-terminal with immunogenic robustness linkers. The mRNA vaccine is translated into a protein-based vaccine by the host body's ribosomes. Their comprehensive computational findings, including physicochemical, structural, and 3D refinement analyses, substantiated the stability and quality of the translated vaccine. Molecular docking and simulation revealed a strong and stable binding affinity of vaccine immunization with immune cells' pattern recognition receptors (TLR4). Immune simulations demonstrated a potent primary immune response characterized by a gradual increase in immunoglobulins and a corresponding decline in antigen concentration. This bioinformatics-driven study presents a promising HIV-1 mRNA vaccine candidate, underscoring the need for further experimental validation through preclinical and clinical trials. At the same time, its methodologies hold the potential for addressing other challenging infectious diseases, thereby impacting vaccinology broadly.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"16 ","pages":"1480025"},"PeriodicalIF":5.7,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12106336/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144157739","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":"Janus kinase inhibitors for alopecia areata: a review of clinical data.","authors":"Yutong Sun, Qian Li, Yanli Zhang, Yaling Liu","doi":"10.3389/fimmu.2025.1577115","DOIUrl":"10.3389/fimmu.2025.1577115","url":null,"abstract":"<p><p>Alopecia areata (AA) is an autoimmune disease characterized by inflammatory and non-scarring hair loss, mediated by CD8+ T cells and primarily affecting hair follicles. Janus kinase (JAK) inhibitors selectively inhibit JAK, block the signal transducer and activator of transcription pathway, and often interfere with T-cell-mediated inflammatory cytokine pathways. They are a class of targeted anti-inflammatory drugs that can promote the activation of hair follicle stem cells. Studies have shown that JAK inhibitors exhibited good efficacy and safety in the treatment of AA, with fewer serious side effects. This article reviews the mechanism of action of JAK inhibitors in the treatment of AA and the effects and side effects of representative drugs.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"16 ","pages":"1577115"},"PeriodicalIF":5.7,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12106550/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144157887","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":"Cost-effectiveness analysis of first-line cadonilimab plus chemotherapy in HER2-negative advanced gastric or gastroesophageal junction adenocarcinoma.","authors":"Zhifeng Zhou, Yanqing Yang, Shaofang Chen, Maojin You","doi":"10.3389/fimmu.2025.1575627","DOIUrl":"10.3389/fimmu.2025.1575627","url":null,"abstract":"<p><strong>Background: </strong>The COMPASSION-15 trial demonstrated that cadonilimab plus chemotherapy (CAD-CHM) confers clinical benefits over placebo plus chemotherapy (PLA-CHM) as a first-line treatment for human epidermal growth factor receptor 2 (HER2)-negative advanced gastric or gastroesophageal junction (G/GEJ) adenocarcinoma. However, the introduction of cadonilimab substantially elevates treatment costs, and its cost-effectiveness relative to PLA-CHM remains undetermined. This study evaluates the cost-effectiveness of CAD-CHM compared with PLA-CHM from the perspective of the Chinese healthcare system.</p><p><strong>Methods: </strong>A Markov model with three health states was developed to assess the cost-effectiveness of CAD-CHM in HER2-negative advanced G/GEJ adenocarcinoma. Clinical efficacy data were sourced from the COMPASSION-15 trial, while drug costs were calculated based on national tender prices, and additional costs and utility values were extracted from published literature. The analysis encompassed the overall population, as well as subgroups stratified by programmed death ligand 1 (PD-L1) combined positive score (CPS) ≥ 5 and CPS < 5. Outcomes included total costs, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios (ICERs). Sensitivity analyses were conducted to evaluate model robustness.</p><p><strong>Results: </strong>The ICER of CAD-CHM was $67,378.09 per QALY in the overall population, $48,433.34 per QALY in the PD-L1 CPS ≥ 5 subgroup, and $78,463.86 per QALY in the PD-L1 CPS < 5 subgroup. Key determinants influencing model outcomes included patient weight, cadonilimab cost, and the utility value of progression-free survival. Across all groups, CAD-CHM resulted in an ICER exceeding the willingness-to-pay threshold of $41,511 per QALY, with a 0% probability of cost-effectiveness compared with PLA-CHM.</p><p><strong>Conclusion: </strong>From the perspective of the Chinese healthcare system, CAD-CHM is not cost-effective as a first-line treatment for HER2-negative advanced G/GEJ adenocarcinoma, either in the overall population or in subgroups stratified by PD-L1 CPS status, compared with chemotherapy alone.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"16 ","pages":"1575627"},"PeriodicalIF":5.7,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12106304/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144157948","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":"Molecular subtypes based on ferroptosis-related genes and tumor microenvironment infiltration characterization in small cell lung cancer.","authors":"Xin Wang, Zhenyi Xu, Zhen Lin, Dawei Wu, Yu Tang, Zhihua Pei, Yibo Gao, Jie He","doi":"10.3389/fimmu.2025.1574434","DOIUrl":"10.3389/fimmu.2025.1574434","url":null,"abstract":"<p><strong>Background: </strong>Ferroptosis is an iron-dependent form of regulated cell death associated with cancer. However, the characteristics of ferroptosis in small cell lung cancer (SCLC) are still uncertain. This study aimed to explore the application value of ferroptosis-related genes (FRGs) classification in prognosis and characteristics prediction to provide clues for targeted SCLC therapy.</p><p><strong>Method: </strong>We systematically characterized mRNA expression and genetic alterations of FRGs in SCLC, evaluating their expression pattern in 181 samples from 3 datasets. Unsupervised clustering analysis was performed to identify the molecular subtypes based on FRGs. We then conducted association analyses between FRG subtypes and various tumor microenvironment (TME) characteristics, traditional key transcript factor subtypes, clinical features, transcriptional and post-transcriptional regulation, drug response, and the efficacy of immunotherapy. Furthermore, the novel classification was validated in an independent cohort of 34 samples from Beijing.</p><p><strong>Result: </strong>In this study, we identified three distinct ferroptosis subtypes in SCLC: S1, S2, and S3. We found that patients in S2 had the poorest prognosis. The FRG classification was correlated with the NOTCH pathway, MYC pathway, Neuroendocrine (NE), and epithelial-to-mesenchymal transition (EMT) process. Additionally, the FRG classification was strongly associated with TME 4 subtypes. To validate the classification, we employed an independent cohort. The FRG classification could also help to guide the prediction of chemical drugs. Finally, the heatmap showed the landscape of FRG subtypes, TME subtypes, NE subtypes, key transcription subtypes, age, gender, and stage.</p><p><strong>Conclusion: </strong>Our identification of new SCLC subtypes provides novel insights into tumor biology and has potential clinical implications for the management of SCLC.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"16 ","pages":"1574434"},"PeriodicalIF":5.7,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12106331/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144157955","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}