ImmunoTargets and Therapy最新文献

{"title":"Multi-Dimensional Characterization of Programmed Cell Death Patterns for Prognostic Stratification and Therapeutic Insights in Sepsis.","authors":"Chen Zhou, Yunmeng Bai","doi":"10.2147/ITT.S555950","DOIUrl":"10.2147/ITT.S555950","url":null,"abstract":"<p><strong>Background: </strong>Sepsis is a complex and heterogeneous syndrome characterized by dysregulated immune responses and multiple forms of programmed cell death (PCD). Comprehensive understanding of the PCD landscape may provide insights into prognosis and therapeutic targets, whereas its role in sepsis is not well-explored.</p><p><strong>Methods: </strong>Using the microarray dataset for sepsis (GSE65682), we systematically profiled 14 PCD patterns in sepsis and stratified patients into molecular subtypes with distinct immune landscapes and clinical outcomes. PCD-related prognostic signature was developed and validated across multiple cohorts. Single-cell and multi-organ transcriptomic analyses were conducted to elucidate cellular heterogeneity and temporal dynamics. Molecular docking was used to explore interactions between active compounds of Simiao Yongan Decoction (SMYAD) and key PCD-related proteins.</p><p><strong>Results: </strong>Two clusters with differential transcriptional programs and immune infiltration patterns were identified, in which Cluster 1 showed poorer prognosis. We then developed a seven-gene signature (<i>ELANE, CTSG, MPO, CAMP, TFRC, IL1B, CASP5</i>) that effectively stratified patients by survival outcomes, with robust predictive performance across independent datasets. Neutrophils, monocytes, plasma, and dendritic cells were major mediators of PCD-associated immune dysregulation, in which neutrophils showing the strongest response. Temporal transcriptomics revealed peak expression of prognostic genes in bone marrow and peripheral blood within three days post-onset, suggesting an early therapeutic window. Finally, molecular docking indicated that SMYAD compounds may target PCD proteins (<i>MPO, ELANE, IL1B</i>) and modulate immune responses.</p><p><strong>Conclusion: </strong>This study delineates the multi-dimensional role of PCD in sepsis, establishes a reliable prognostic model with strong predictive value, and highlights SMYAD as a potential multi-target therapy. These findings provide new avenues for risk stratification and suggest the promise of integrating PCD biology with adjunctive immunomodulatory strategies.</p>","PeriodicalId":30986,"journal":{"name":"ImmunoTargets and Therapy","volume":"14 ","pages":"1313-1331"},"PeriodicalIF":4.4,"publicationDate":"2025-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12628821/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145565658","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}

{"title":"Clinical Risk Stratification and Modifiable Risk Factors for Hepatitis B Virus-Related Follicular Lymphoma.","authors":"Yuwei Deng, Zhenyuan Jia, Huilai Zhang, Xiaosan Zhang, Lihong Liu, Xianhuo Wang, Hongtao Song, Zirong Zhang, Caili Liu, Qingyuan Zhang, Jianli Ma","doi":"10.2147/ITT.S543117","DOIUrl":"10.2147/ITT.S543117","url":null,"abstract":"<p><strong>Background: </strong>Hepatitis B virus (HBV) infection (surface antigen positive, HBsAg+) has been related to the increased risk in follicular lymphoma (FL). The further understanding of features in HBV-associated FL remains lacking.</p><p><strong>Methods: </strong>We explored clinical risk factors in HBsAg-positive patients from multicentric clinical investigation retrospectively (n = 276) and integrated HBV-related factors into Follicular Lymphoma International Prognostic Index (FLIPI) scoring system for risk prediction. The methylation profiles in pre- and paired HBsAg+FL occurring progression of disease within 2 years (POD24) were determined using the Human Methylation 850K BeadChip platform. Bulk RNA sequencing was performed for gene expression in samples from the same patient and confirmed using Myc^Cd19Cre C57BL/6J chimera mice.</p><p><strong>Results: </strong>We found that HBsAg+ FL with a higher incidence of POD24. The high HBV-DNA load (>10⁵ copies/mL) was identified as a pivotal risk factor. HBsAg+ FL with the rapidly decreasing viral load showed lower incidence of POD24 than those without viral control (<i>P</i> = 0.026). Integrated risk stratification incorporating HBV-related clinical parameters based on FLIPI scoring systems had potential predictive value for high-risk patients (AUC = 0.616, <i>P</i> = 0.002). The methylation profiles in pre-POD24-HBsAg+FL and paired POD24-HBsAg+FL showed distinguished signatures of methylated <i>KMT2A</i>, <i>EP300-AS1</i>, <i>ARID1B</i>, <i>MHC I</i> class molecular genes related to tumor cells, and <i>TNFRSF1A</i>, <i>LTA</i>, <i>IQCE</i> genes related to immune cells. Of note, we confirmed that the crucial CXCR5 mRNA expression with specific methylated regions was inversely correlated to featured MYC mRNA expression as \"trans\" regulation in both POD24-HBsAg+FL and <i>Myc^Cd19Cre</i> lymphoma model.</p><p><strong>Conclusion: </strong>Integrated clinicopathological features into prediction system may provide precise risk stratification for HBV-positive FL. Modifiable DNA methylation acts as the potential targets for the combined treatment strategy to delay POD24 occurrence.</p>","PeriodicalId":30986,"journal":{"name":"ImmunoTargets and Therapy","volume":"14 ","pages":"1293-1312"},"PeriodicalIF":4.4,"publicationDate":"2025-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12620592/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145551307","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}

{"title":"Emerging Role of MDSCS as Novel Biomarkers and Therapeutic Targets for Cancer Immunotherapy.","authors":"S Silva-Romeiro, Rocio Del Carmen Flores-Campos, María Luisa Sánchez-León, V Sánchez-Margalet, Luis De la Cruz-Merino","doi":"10.2147/ITT.S485642","DOIUrl":"10.2147/ITT.S485642","url":null,"abstract":"<p><p>Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population of immature myeloid cells that accumulate under pathological conditions such as cancer, where they contribute to immune evasion, tumor progression, and resistance to therapy. These cells exert potent immunosuppressive effects by inhibiting T cell activation, inducing regulatory T cells, modulating antigen-presenting cells, and shaping an immunosuppressive tumor microenvironment (TME). Their suppressive functions involve multiple mechanisms, including amino acid depletion, production of reactive oxygen and nitrogen species, expression of immune checkpoint ligands, and secretion of immunoregulatory cytokines such as IL-10 and TGF-β. Besides these immune-related roles, MDSCs also promote tumor growth through non-immunological mechanisms, including the stimulation of angiogenesis and undergoing metabolic reprogramming. These adaptations support their survival and function in the hostile TME. Given their multifaceted role in cancer, MDSCs represent a promising target for therapeutic intervention. Furthermore, their abundance and dynamic modulation during treatment confer them tremendous potential as biomarkers to monitor therapy efficacy and stratify patients. This review provides a comprehensive overview of MDSC biology, their mechanisms of action, and their emerging clinical relevance as biomarkers and therapeutic targets. We also explore current strategies aimed at targeting MDSCs, including their depletion, inhibition of recruitment, functional blockade, and promotion of their differentiation into mature myeloid cells. Integrating these approaches with existing cancer therapies holds great promise for enhancing antitumor immunity and overcoming resistance in both solid tumors and hematologic malignancies.</p>","PeriodicalId":30986,"journal":{"name":"ImmunoTargets and Therapy","volume":"14 ","pages":"1267-1291"},"PeriodicalIF":4.4,"publicationDate":"2025-11-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12617971/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145542788","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}

{"title":"Understanding and Managing Hyper IgE Syndromes.","authors":"Zeynep Meric, Muhammed Aydin, Dilan Demir Gumus, Esra Yucel, Ayca Kiykim","doi":"10.2147/ITT.S532287","DOIUrl":"10.2147/ITT.S532287","url":null,"abstract":"<p><p>Hyper-IgE syndromes represent an increasingly recognized and heterogeneous group of disorders characterized phenotypically by eczema, recurrent infections, and markedly elevated serum IgE levels. The identification of novel molecular defects in recent years has complicated definitive diagnosis, underscoring the genetic and clinical diversity of this group. In addition to immunological abnormalities, non-immunological manifestations-particularly those affecting connective tissue-contribute to significant comorbidities. The primary objectives of management are to control infections, prevent long-term complications, and improve quality of life. In this review, we summarize the clinical and laboratory features of disorders currently classified under hyper-IgE syndromes according to the most recent International Union of Immunological Societies framework and provide perspectives on their management.</p>","PeriodicalId":30986,"journal":{"name":"ImmunoTargets and Therapy","volume":"14 ","pages":"1233-1245"},"PeriodicalIF":4.1,"publicationDate":"2025-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12596842/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145490146","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}

{"title":"Soluble Programmed Cell Death-1: A Potential Predictor of HBsAg Loss in Pediatric Patients with Chronic Hepatitis B Undergoing Peginterferon Therapy.","authors":"Guifeng Yang, Yifan Gan, Muye Xia, Qunfang Fu, Mingxia Zhang, Kangxian Luo, Zhanhui Wang","doi":"10.2147/ITT.S541485","DOIUrl":"10.2147/ITT.S541485","url":null,"abstract":"<p><strong>Purpose: </strong>Soluble programmed cell death-1 (sPD-1) level can predict hepatitis B surface antigen (HBsAg) loss in adult chronic hepatitis B (CHB) patients. However, whether sPD-1 level can serve as a potential seromarker for predicting HBsAg loss in pediatric patients remained to determine.</p><p><strong>Patients and methods: </strong>Ninety-two pediatric HBeAg-positive CHB patients who received peginterferon (PegIFN) therapy with available serum samples were studied retrospectively. The average follow-up time was 45.0 months. Virological biomarkers and sPD-1 were serially measured.</p><p><strong>Results: </strong>A total of 45 (48.9%) children achieved HBsAg loss at the end of treatment (EOT), and 84.4% (38/45) of them remained HBsAg-negative at the end of follow-up. At baseline, sPD-1 levels were comparable between patients who subsequently achieved HBsAg loss and those who did not (<i>P</i> = 0.217). However, a significantly more pronounced increase in sPD-1 levels was observed during PegIFN treatment in the HBsAg loss group (<i>P_trend</i> < 0.001). Consequently, at weeks 12, 24, and EOT, sPD-1 levels were significantly higher in children with HBsAg loss compared to those without (<i>P</i> < 0.001 at all time-points). In ROC curve analysis, sPD-1 had strong discriminatory ability for HBsAg loss at weeks 12 and 24, with area under ROC scores of 0.842 (95% CI, 0.744-0.946) and 0.863 (95% CI, 0.758-0.969), respectively, slightly lower than HBsAg but higher than HBV DNA.</p><p><strong>Conclusion: </strong>Early on-treatment serum sPD-1 level has a potential predictive value for HBsAg loss in pediatric patients with HBeAg-positive CHB, which might provide a clue to optimize the management of PegIFN therapy. However, a prospective, multi-center study is warranted for further validation.</p>","PeriodicalId":30986,"journal":{"name":"ImmunoTargets and Therapy","volume":"14 ","pages":"1223-1231"},"PeriodicalIF":4.4,"publicationDate":"2025-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12595934/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145483136","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}

{"title":"Profiling Shared Cytotoxic Immune Signatures in SLE-Associated Coronary Injury Through Transcriptomics and Machine Learning.","authors":"Yongkang Chen, Shuk Ming Tso, Feng Wu, Yue Xu, Liyan Cui","doi":"10.2147/ITT.S539756","DOIUrl":"10.2147/ITT.S539756","url":null,"abstract":"<p><strong>Purpose: </strong>This study investigated shared molecular pathways linking systemic lupus erythematosus (SLE) and coronary artery disease (CAD) to uncover mechanisms of coronary injury in SLE.</p><p><strong>Patients and methods: </strong>Bulk transcriptomic datasets (GSE45291 for SLE, GSE61145 for CAD) were analyzed to identify differentially expressed genes (DEGs), immune cell infiltration patterns, and co-expression networks. A diagnostic model was constructed and validated using external cohorts (GSE49454 for SLE, GSE179789 for CAD). Machine learning prioritized core genes, validated in both external cohorts and in SLE patients with coronary injury (GSE264125). Cellular localization and intercellular communication were explored by analyzing single-cell RNA-seq data (GSE135779). qPCR was used to validate the gene expression in peripheral blood mononuclear cells (PBMCs) from patients.</p><p><strong>Results: </strong>We identified 146 common DEGs enriched in immune pathways related to cell toxicity, and found shared dysregulation in cytotoxic lymphocytes such as natural killer (NK) cells and CD8⁺ T cells. Through co-expression analysis and DEG intersection, we pinpointed 11 hub genes (eg, GZMK, KLRK1, GNLY). A diagnostic model based on these genes showed strong performance (SLE: AUC 0.881 training, 0.666 validation; CAD: AUC 0.897 training, 0.781 validation). Machine learning highlighted GZMK and KLRK1 as core genes, which were further validated for their combined diagnostic utility (AUC: 0.782-1.000) in SLE-related coronary injury. Single-cell analysis revealed that these genes are primarily active in cytotoxic CD8⁺ T cells and NK cells, with GZMK linked to CLEC-mediated signaling and KLRK1 to HLA activation. Finally, we confirmed higher expression of these genes in blood cells from SLE patients with coronary artery disease using qPCR.</p><p><strong>Conclusion: </strong>SLE and CAD share a cytotoxic lymphocyte-driven molecular axis, with GZMK/KLRK1-mediated immune dysregulation as a key contributor to coronary injury in SLE. GZMK and KLRK1 may represent promising biomarkers for early detection and risk stratification of SLE-associated coronary complications. Notably, the discrimination (AUC=1.000) was observed in a limited subgroup of SLE patients with coronary microvascular dysfunction (n=4), warranting further validation in expanded cohorts.</p>","PeriodicalId":30986,"journal":{"name":"ImmunoTargets and Therapy","volume":"14 ","pages":"1247-1266"},"PeriodicalIF":4.4,"publicationDate":"2025-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12595958/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145483114","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}

{"title":"Glucose Metabolic Reprogramming of Macrophages Against <i>Mycobacterium tuberculosis</i> Infection.","authors":"Tianhui Liu, Zeliang Yang, Jing Tong, Mengqiu Gao, Yu Pang","doi":"10.2147/ITT.S552746","DOIUrl":"10.2147/ITT.S552746","url":null,"abstract":"<p><p>Tuberculosis (TB) is a global infectious disease caused by <i>Mycobacterium tuberculosis</i> (<i>Mtb</i>). Serving as the primary effector cells, macrophages play a crucial role in host immune responses against <i>Mtb</i>. During <i>Mtb</i> infection, macrophages undergo extensive metabolic reprogramming, notably glycolysis, the pentose phosphate pathway (PPP) and the tricarboxylic acid (TCA) cycle, to adapt to the challenges posed by the pathogen, with glucose metabolic rewiring being particularly critical. This review focuses on the dynamic reprogramming of glucose metabolism in macrophages during <i>Mtb</i> infection, highlighting how metabolic adjustments influence the activation state, polarization, and functional capacity of macrophages. Furthermore, we explore the role of glucose metabolic reprogramming in shaping the immune responses against <i>Mtb</i>, particularly its contribution to granuloma formation and maintenance. By understanding the intricate interplay between metabolic rewiring and immune function, we discuss the therapeutic potential of targeting glucose metabolic pathways in macrophages as a novel strategy for TB treatment. Overall, this review emphasizes the need for a deeper understanding of the relationship between glucose metabolism reprogramming and the biological function of <i>Mtb</i>-infected macrophages and the development of novel immunometabolic therapies-such as metformin (AMPK activator) or PKM2 modulators already used in oncology- to improve the outcomes of TB patients.</p>","PeriodicalId":30986,"journal":{"name":"ImmunoTargets and Therapy","volume":"14 ","pages":"1209-1221"},"PeriodicalIF":4.4,"publicationDate":"2025-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12584850/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145452986","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}

{"title":"Dramatic Clinical Response to a Novel Form of Cell Therapy SL-28 in a Patient with Prostate Cancer and Bone Metastasis: A Case Report.","authors":"Victor Tetz, Kristina Kardava, Olzhas Shulenbayev, Maria Vecherkovskaya, Alireza Khodadadi-Jamayran, Aristotelis Tsirigos, George Tetz","doi":"10.2147/ITT.S547989","DOIUrl":"10.2147/ITT.S547989","url":null,"abstract":"<p><strong>Purpose: </strong>Prostate cancer is the most common malignancy among older man and often a challenge owing to its rapid spread and age-related comorbidities. SL-28 (Leukocyte-Tells) is a novel cell therapy that uses allogeneic leukocytes whose anticancer activity is altered ex vivo using the recently discovered Universal Receptive System.</p><p><strong>Patients and methods: </strong>A 79-year-old man with Т2сNOMx1, Gleason 7 (3+4) adenocarcinoma of the prostate, with a total PSA level of 10.6 ng/mL and free PSA:total PSA ratio of 11.4% received hormone therapy. Due to an insufficient clinical response and poor tolerance to the therapy, the patient underwent novel allogeneic SL-28 cell therapy.</p><p><strong>Results: </strong>SL-28 therapy was well-tolerated, with no serious adverse effects. The levels of laboratory markers of prostate cancer, such as prostate-specific antigen, gradually improved from the second week of SL-28 therapy. Complete responses, including the resolution of bone metastasis within 4 months of therapy, were confirmed by computed tomography and histology.</p><p><strong>Conclusion: </strong> SL-28 was efficient and safe approach in a patient with stage IV prostate cancer, supporting its potential in an allogeneic cell therapy for advanced malignancies.</p>","PeriodicalId":30986,"journal":{"name":"ImmunoTargets and Therapy","volume":"14 ","pages":"1201-1207"},"PeriodicalIF":4.4,"publicationDate":"2025-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12579837/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145439226","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}

{"title":"Sorafenib Combined with Tislelizumab and Transarterial Chemoembolization for Advanced-Stage Hepatocellular Carcinoma: A Phase II Study.","authors":"Licong Liang, Jingwen Zhou, Jingjun Huang, Yongjian Guo, Zhimei Zhou, Ye Chen, Liteng Lin, Xiaoyang Hong, Wenbo Shi, Zhaoyi Lin, Juan Liu, Kangshun Zhu, Wensou Huang, Mingyue Cai","doi":"10.2147/ITT.S543741","DOIUrl":"10.2147/ITT.S543741","url":null,"abstract":"<p><strong>Purpose: </strong>To evaluate the efficacy and safety of sorafenib combined with tislelizumab (a programmed death-1 inhibitor) and transarterial chemoembolization (TACE) in patients with advanced-stage hepatocellular carcinoma (HCC).</p><p><strong>Patients and methods: </strong>This was a single-center, single-arm phase II trial. Patients with HCC at Barcelona Clinic Liver Cancer stage C were recruited. Treatment with sorafenib (400 mg orally twice daily) and tislelizumab (200 mg intravenously every 3 weeks) was initiated 3-7 days after the first TACE procedure. Repeated TACE was performed on-demand. The primary endpoint of this study was overall survival (OS).</p><p><strong>Results: </strong>Thirty patients were enrolled. The median OS for the patients was 18.3 (95% CI = 14.6-22.0) months, with 12-, 18-, and 24-month OS rates of 90.0%, 54.0%, and 28.3%, respectively. The objective response rate was 53.3% per modified Response Evaluation Criteria in Solid Tumors (mRECIST) and 20.0% per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1). The disease control rate was 86.7% per mRECIST/RECIST 1.1. The median progression-free survival was 6.8 (95% CI = 4.5-9.0) months per mRECIST/RECIST 1.1. The median duration of response was 7.1 (95% CI = 6.1-8.1) months per mRECIST (n = 16) and 4.4 (95% CI = 0.9-7.9) months per RECIST 1.1 (n = 6). Treatment-related adverse events (TRAEs) occurred in 28 patients (93.3%), and grade 3 TRAEs were observed in 11 patients (36.7%). There were no grade 4/5 TRAEs.</p><p><strong>Conclusion: </strong>Sorafenib combined with tislelizumab and TACE showed promising antitumor activities with a manageable safety profile in patients with advanced-stage HCC. These preliminary findings warrant further evaluation in Phase III randomized trials.</p>","PeriodicalId":30986,"journal":{"name":"ImmunoTargets and Therapy","volume":"14 ","pages":"1187-1200"},"PeriodicalIF":4.4,"publicationDate":"2025-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12571927/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145432485","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}

{"title":"Regulatory Mechanisms of Co-Inhibitory Receptors in Tuberculosis Immunity: Implications for Therapeutic Targets.","authors":"Huicong Liu, Haoran Li, Shanshan Li, Yuanyuan Shang, Shenjie Tang, Yu Pang","doi":"10.2147/ITT.S540343","DOIUrl":"10.2147/ITT.S540343","url":null,"abstract":"<p><p>Tuberculosis (TB) is a chronic infectious disease caused by <i>Mycobacterium tuberculosis</i> (<i>Mtb</i>). Despite significant advancements in anti-tuberculosis treatment strategies in recent years, TB remains a major infectious disease threat worldwide. Chronic <i>Mtb</i> infection drives T cell exhaustion-characterized by upregulated co-inhibitory receptors-which correlates with TB chronicity, treatment failure, and relapse. Immune checkpoint inhibitors (ICIs) targeting co-inhibitory receptors have achieved groundbreaking progress in the treatment of various malignancies. However, their application in the field of tuberculosis remains controversial. This study provides a comprehensive analysis of TB disease assessment and treatment from the perspective of T cell exhaustion. We investigate the correlation between co-inhibitory receptor expression levels and both disease activity and progression. Furthermore, we analyze the dual impact of targeting these receptors on anti-TB immunity: While blockade of co-inhibitory receptors in T cell exhaustion states restores anti-tuberculosis immunity, excessive inhibition-particularly in hyperimmune conditions-induces detrimental hyperinflammation, exacerbating tissue damage and disrupting immune homeostasis, ultimately worsening clinical outcomes. To address this duality, we emphasize the necessity of personalized immunotherapy strategies based on individual immune profiling, alongside developing novel co-inhibitory receptor blockers and immune modulatory vaccines. This review presents a novel perspective on the application of targeting co-inhibitory receptors in tuberculosis treatment, which will advance the development and application of immunotherapy.</p>","PeriodicalId":30986,"journal":{"name":"ImmunoTargets and Therapy","volume":"14 ","pages":"1169-1185"},"PeriodicalIF":4.4,"publicationDate":"2025-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12560657/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145402197","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}