ImmunoTargets and Therapy最新文献

{"title":"Efficiency and Safety of HAIC Combined with Lenvatinib and PD-1 Inhibitor for Advanced Hepatocellular Carcinoma with Lung Metastasis: A Multicenter Propensity Score Matching Analysis.","authors":"Song Chen, Ning Wang, Yi Xiao, Xiongying Jiang, Feng Shi, Hongjie Cai, Shuangyan Tang, Wenbo Guo, Wenquan Zhuang","doi":"10.2147/ITT.S542811","DOIUrl":"10.2147/ITT.S542811","url":null,"abstract":"<p><strong>Purpose: </strong>This study aimed to evaluate the clinical efficiency and safety of hepatic arterial infusion chemotherapy (HAIC) combined with lenvatinib and programmed cell death protein-1 (PD-1) inhibitor for patients with hepatocellular carcinoma (HCC) and lung metastasis.</p><p><strong>Methods: </strong>In this multicenter retrospective study, treatment-naive patients with advanced (BCLC stage C) HCC and lung metastases who received lenvatinib and PD-1 inhibitor - with or without HAIC - between January 2019 and January 2024 were reviewed. Propensity score matching (PSM) was applied to balance baseline characteristics between the two groups. The primary endpoint was overall survival (OS). Secondary endpoints included progression-free survival (PFS), objective response rate (ORR), and disease control rate (DCR) according to RECIST 1.1 criteria, as well as adverse events (AEs).</p><p><strong>Results: </strong>A total of 422 eligible patients were included, with 169 receiving HAIC (HLP group) and 253 receiving lenvatinib plus PD-1 inhibitor (LP group). After 1:1 PSM, 151 patients were matched in each group. The HLP group demonstrated significantly longer median OS compared to the LP group (26.0 <i>versus</i> 8.4 months; hazard ratio [HR]: 0.36; 95% confidence interval [CI]: 0.27-0.49; <i>P</i> < 0.001). Median PFS was also improved in the HLP group (7.6 <i>versus</i> 5.5 months; HR: 0.77; 95% CI: 0.59-1.00; <i>P</i> = 0.048). ORR and DCR were significantly higher in the HLP group (ORR: 47.7% <i>versus</i> 20.5%, <i>P</i> < 0.001; DCR: 86.1% <i>versus</i> 72.2%, <i>P</i> = 0.003). Although the HLP group experienced a higher incidence of both all-grade and grade 3/4 AEs, all were manageable, and no grade 5 events occurred.</p><p><strong>Conclusion: </strong>HAIC combined with lenvatinib and PD-1 inhibitor shows promise as a treatment for advanced HCC with lung metastases, offering improved prognosis and a manageable safety profile.</p>","PeriodicalId":30986,"journal":{"name":"ImmunoTargets and Therapy","volume":"14 ","pages":"953-965"},"PeriodicalIF":4.4,"publicationDate":"2025-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12415092/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145030913","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":"Machine Learning-Derived Neddylation Gene Signature for Predicting Prognosis and Immunotherapy Benefits in Colorectal Cancer.","authors":"Guangda Yang, Jieming Xiao, Huixiang He, Jing Wang, Zhichao Wang, Liumeng Jian, Qianya Chen","doi":"10.2147/ITT.S532644","DOIUrl":"10.2147/ITT.S532644","url":null,"abstract":"<p><strong>Background: </strong>Colorectal cancer (CRC) is a major cause of cancer deaths globally, mainly due to treatment resistance. Neddylation, a key post-translational modification, is linked to tumor growth and immune response, offering potential therapeutic targets, though its role in CRC is not well-explored.</p><p><strong>Methods: </strong>We examined neddylation-related genes (NRGs) across cell subtypes using CRC scRNA-seq data from the TISCH database. Unsupervised clustering of TCGA and GEO bulk RNA-seq data identified various neddylation patterns. A neddylation-related gene signature (NRGS) was developed using ten machine-learning algorithms and validated externally. The study compared biofunctions, including functional analysis, immune cell infiltration, genomic mutations, enrichment analysis, and responses to immunotherapy and chemotherapy, between high- and low-risk groups defined by the NRGS model.</p><p><strong>Results: </strong>scRNA-seq analysis showed that the high neddylation score group had more malignant and diverse immune and stromal cells, with activated pathways aiding tumor growth and spread. We identified two neddylation patterns: Cluster A and Cluster B. Cluster B, associated with worse survival, had more immunosuppressive cells and increased tumor progression. We developed a neddylation-related gene signature (NRGS) using ten machine-learning algorithms, which accurately predicted outcomes. Higher risk scores correlated with poorer survival, with AUCs of 0.979, 0.989, and 0.996 for 1-year, 2-year, and 3-year OS in the training cohort. The NRGS was linked to higher recurrence or metastasis, advanced disease stage, and independently predicted OS risk. Patients with high NRGS may resist immunotherapy and standard chemotherapy.</p><p><strong>Conclusion: </strong>The NRGS could predict outcomes and responses to immunotherapy and chemotherapy in CRC patients, aiding personalized treatment, though further validation is needed.</p>","PeriodicalId":30986,"journal":{"name":"ImmunoTargets and Therapy","volume":"14 ","pages":"931-952"},"PeriodicalIF":4.4,"publicationDate":"2025-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12396537/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144971956","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":"Ultrasound-Mediated Non-Specific Splenic Immunopotentiation to Elicit Broad-Spectrum Anti-Neoplastic Effects.","authors":"Wei Dong, Guihu Wang, Senyang Li, Qian Wang, Wenjuan Li, Heyuan Liu, Yingxue Liang, Zhe Zhou, Xinrui He, Wenlei Guo, Jianing Yuan, Yichao Chai, Jing Geng, Zongfang Li","doi":"10.2147/ITT.S534444","DOIUrl":"10.2147/ITT.S534444","url":null,"abstract":"<p><strong>Background: </strong>Splenic immunomodulation triggered by ultrasound shows a significant anti-inflammatory effect against various inflammatory diseases, whose mechanism is mainly attributable to the activation of cholinergic anti-inflammatory pathway (CAP). However, the potential role and underlying mechanism of splenic ultrasound stimulation in cancer management have been rarely reported and superficially defined.</p><p><strong>Methods: </strong>Following optimization of ultrasonic parameters, this study evaluated the anti-tumor efficacy of splenic sonication across multiple tumor models (eg, orthotopic H22 hepatocellular carcinoma (HCC), orthotopic Hepa1-6 HCC, and subcutaneous 4T1 breast cancer), and applied flow cytometry to quantify dynamic alterations in immune cell populations. Furthermore, in orthotopic H22 HCC models, this study employed fluorescence-activated cell sorting, RNA sequencing, splenic nerve blockade via absolute ethanol ablation, and in vitro Ca²⁺ flux assays to delineate the mechanisms underlying ultrasound-mediated splenic anti-tumor immunity.</p><p><strong>Results: </strong>This study first assessed the therapeutic effect of focused ultrasound precisely targeting the spleen (FUS sti. spleen) on various tumors at specific ultrasonic doses. It fully demonstrated that FUS directly stimulated splenic immune cell proliferation and activation (especially NK and CD8 T cells) rather than CAP excitation to modulate splenic immune function. Particularly, NK cells are much more indispensable and important in responding to FUS stimulation for cancer suppression than CD8 T cells. RNA sequencing of NK and CD8 T cells, as well as in vitro experiments revealed that FUS firstly regulated calcium-related signaling pathways to further modulate others, such as PI3K-AKT, Rap1, and Hippo pathways to promote immune cell proliferation, migration and activation to suppress cancer cell deterioration. Particularly, FUS sti. spleen and FUS intervention on the tumor synergistically induced the best tumor suppression than each of the two taken individually.</p><p><strong>Conclusion: </strong>FUS sti. spleen facilitated immunocyte proliferation and activation through altering calcium-dependent signaling rather than CAP excitation to modulate anti-tumor immunity, indicating substantial clinical translation potential.</p>","PeriodicalId":30986,"journal":{"name":"ImmunoTargets and Therapy","volume":"14 ","pages":"901-930"},"PeriodicalIF":4.4,"publicationDate":"2025-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12393091/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144972016","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":"Calcitriol and Tacalcitol Modulate Th17 Differentiation Through Osteopontin Receptors: Age-Dependent Insights from a Mouse Breast Cancer Model.","authors":"Aleksandra Strzykalska-Augustyniak, Mateusz Psurski, Honorata Zachary, Beata Filip-Psurska, Dagmara Kłopotowska, Magdalena Milczarek, Marta Świtalska, Martyna Stachowicz-Suhs, Natalia Łabędź, Aleksandra Ziemblicka, Michalina Gos, Joanna Wietrzyk","doi":"10.2147/ITT.S537852","DOIUrl":"10.2147/ITT.S537852","url":null,"abstract":"<p><strong>Purpose: </strong>Beyond its direct anticancer effects in breast cancer (BC), vitamin D₃ (VD₃) also modulates tumor progression and metastasis through immune mechanisms. T-helper 17 (Th17) cells may play a key role in these effects. This study investigates how VD₃ influences Th17 differentiation in 4T1 and 67NR murine BC models.</p><p><strong>Methods: </strong>Calcitriol or tacalcitol was administered to young and aged mice bearing 4T1 or 67NR tumors. Tumor growth, angiogenesis, and metastasis were evaluated. CD4⁺ lymphocytes isolated from tumors and other tissues were analyzed by flow cytometry for IL-17 and osteopontin (OPN, <i>Spp1</i>) receptors. CD4⁺ splenocytes were separated; gene expression was assessed using qPCR, and protein levels by Western blotting, ELISA. CD3⁺CD4⁺ splenocytes were ex vivo differentiated into Th17 cells with blockade of CD29, CD51, and CD44, followed by flow cytometric analysis of IL-17 and IFNγ expression.</p><p><strong>Results: </strong>Tacalcitol increased metastasis in young mice but decreased it in aged mice with 4T1 tumors. Th17 cell levels in the lungs increased in young mice treated with tacalcitol but declined in aged counterparts. IL-17⁺ and IFNγ⁺ Th17 cells increased upon differentiation from splenocytes of treated mice. CD29 promoted IL-17 expression in tacalcitol-treated mice, while CD51 and CD44 had opposing effects. CD51 blockade reduced IFNγ⁺ Th17 cells in both treatment groups. <i>Spp1</i> expression increased in CD4⁺ lymphocytes, and OPN levels were elevated in induced Th17 cells from tacalcitol-treated young mice, suggesting a role in Th17 activation.</p><p><strong>Conclusion: </strong>CD29 stimulates IL-17 expression in response to tacalcitol, while CD51 and CD44 exert opposing effects. CD51 also mediates IFNγ expression. VD₃-induced modulation of IL-17 and IFNγ in Th17 cells may influence their pro- or anticancer function.</p>","PeriodicalId":30986,"journal":{"name":"ImmunoTargets and Therapy","volume":"14 ","pages":"877-899"},"PeriodicalIF":4.4,"publicationDate":"2025-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12392300/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144972177","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":"Fracture-Induced Immunological Cascades Trigger Rapid Systemic Bone Loss via Osteocyte-Regulated Osteoclastogenesis.","authors":"Lipeng Sun, Shouxiang Kuang, Yang Li, Guodong Wang, Jianmin Sun, Fengge Zhou, Chenggui Zhang","doi":"10.2147/ITT.S533552","DOIUrl":"10.2147/ITT.S533552","url":null,"abstract":"<p><strong>Background: </strong>Rapid bone loss after fracture elevates the risk of subsequent fractures, but the mechanisms remain unclear. IL-6, a key cytokine involved in fracture healing, is markedly upregulated during the immune response after fracture; however, its role in systemic skeletal deterioration remains poorly defined.</p><p><strong>Methods: </strong>In this study, we employed label-free proteomics to identify candidate mediators in vertebral samples following fracture. Next, osteocyte siRNA knockdown and Stattic (STAT3 phosphorylation inhibitor) inhibition were used to investigate IL-6 related signaling pathways. Subsequently, indirect co-cultures of osteocyte with osteoclast or osteoblast were used to evaluate the effects of the IL-6 pathway on bone resorption and formation. Furthermore, fractured mice were treated with MR16-1 (monoclonal anti-mouse IL-6 receptor antibody) or Stattic. Then, trabecular and cortical bone in vertebrae and femur were evaluated at 4, 14, and 28 days post-fracture, including histological analysis of p-STAT3⁺ osteocyte, RANKL expression, and bone formation/resorption markers.</p><p><strong>Results: </strong>In vitro, IL-6 dose-dependently elevated RANKL and p-STAT3 levels in osteocyte and promoted osteoclast activity in co-culture. These effects were suppressed by Stattic and replicated by STAT3 knockdown. In contrast, co-culture of osteocyte with osteoblast exhibited no significant alterations in osteogenic marker expression upon IL-6 exposure, suggesting negligible effects on osteoblast activity. In vivo, MR16-1 reduced trabecular bone loss in the vertebrae and femur after fracture. It also diminished p-STAT3⁺ osteocyte, reduced RANKL expression, and suppressed osteoclast activity without impairing osteoblastogenesis. And Stattic produced a comparable reduction in systemic bone loss and osteoclast overactivation.</p><p><strong>Conclusion: </strong>This study demonstrates that IL-6 drives osteoclast-mediated bone resorption via STAT3-dependent RANKL induction in osteocyte, thereby aggravating post-fracture systemic bone loss. And the findings highlight that modulating the IL-6/STAT3/RANKL axis and targeting osteocyte function may offer a promising therapeutic approach for preventing bone loss and minimizing the risk of fracture recurrence.</p>","PeriodicalId":30986,"journal":{"name":"ImmunoTargets and Therapy","volume":"14 ","pages":"849-875"},"PeriodicalIF":4.4,"publicationDate":"2025-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12377381/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144971988","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":"Comprehensive Insights Into the Role of TRPM4 in Pan-Cancer Progression and Immune Regulation.","authors":"Wuguang Chang, Wuyou Gao, Bin Luo, Youfang Chen, Zhesheng Wen","doi":"10.2147/ITT.S542176","DOIUrl":"10.2147/ITT.S542176","url":null,"abstract":"<p><strong>Background: </strong>Transient receptor potential channel subfamily M member 4 (TRPM4) is a non-selective Na⁺ permeable ion channel that regulates disease processes by enhancing sodium entry and membrane depolarization, but its role in tumors remains underexplored. The purpose of this study is to investigate the role of TRPM4 in pan-cancer progression and immune regulation.</p><p><strong>Methods: </strong>The pan-cancer mRNA expression information of TRPM4 was obtained from TCGA and GTEx, and the protein expression information of TRPM4 was obtained from HPA database. STRING database was utilized to construct the protein-protein interaction network of TRPM4. Gene characterization of TRMP4 was analyzed by GSCA database. The relationship between TRPM4 and immune infiltration characteristics in pan-cancer was analyzed using TCGAplot. Multiple bulk RNA-seq and scRNA-seq datasets treated with PD-(L)1 were used to analyze the relationship between TRPM4 and immunotherapy response. Immunohistochemistry (IHC) and multiplex immunofluorescence (mIHC) were used to validate the expression of TRPM4 in tumor tissue from 19 lung adenocarcinoma patients in relation to the characteristics of immune cell infiltration. In vitro experiments were performed to validate the role of TRPM4 in human breast, lung adenocarcinoma, and esophageal cancer.</p><p><strong>Results: </strong>TRMP4 expression is higher in most tumors than in normal tissues, and the association with prognosis varies with cancer type. TRPM4 correlates with multiple immune checkpoints as well as the degree of immune cell infiltration. Multiple datasets of anti-PD-(L)1 treatment suggested that high expression of TRPM4 was associated with worse treatment prognosis. The IHC and mIHC found that TRPM4 expression was negatively correlated with the level of M1 macrophage and T cell infiltration. <i>In vitro</i> experiments confirmed that knockdown of TRPM4 inhibited proliferation, invasion and migration of human breast, lung and esophageal cancer cells.</p><p><strong>Conclusion: </strong>TRPM4 plays a complex role in tumor progression and immunotherapeutic response, and targeting TRPM4 may offer promising strategies for inhibiting tumor progression and improving immunotherapy resistance.</p>","PeriodicalId":30986,"journal":{"name":"ImmunoTargets and Therapy","volume":"14 ","pages":"831-848"},"PeriodicalIF":4.4,"publicationDate":"2025-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12375349/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144971553","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":"PD-L1/ITGB4 Axis Modulates Sensitivity of Hepatocellular Carcinoma to Sorafenib via FAK/AKT/mTOR Signaling Pathway.","authors":"Tao Zhu, Niandie Cao, Li Tu, Shiqi Ouyang, Zengli Wang, Yong Liang, Shuping Zhou, Xiaolong Tang","doi":"10.2147/ITT.S534782","DOIUrl":"10.2147/ITT.S534782","url":null,"abstract":"<p><strong>Background: </strong>Hepatocellular carcinoma (HCC) frequently develops resistance to sorafenib, a first-line treatment for advanced HCC. While PD-L1 contributes to immune evasion and direct tumor survival, its role in modulating sorafenib resistance via non-immunological pathways remains unclear. This study investigates the PD-L1/ITGB4 axis in regulating sorafenib sensitivity.</p><p><strong>Methods: </strong>Bioinformatics analysis of HCC datasets identified PD-L1/ITGB4 co-expression. Protein interaction was validated via co-immunoprecipitation (Co-IP). Functional impacts on FAK/AKT/mTOR signaling were assessed using kinase inhibitors and gene knockdown in HCC cell lines. Sorafenib sensitivity was evaluated in vitro and in xenograft models with mono- and combination therapies (PD-L1/ITGB4 inhibition ± sorafenib).</p><p><strong>Results: </strong>PD-L1 directly interacts with ITGB4 to activate the FAK/AKT/mTOR signaling pathway, independent of its immune-regulatory functions. This interaction critically mediates sorafenib resistance in HCC, as evidenced by significantly reduced drug sensitivity in PD-L1^high/ITGB4^high cells (<i>p</i> < 0.001). Crucially, genetic knockdown of either PD-L1 or ITGB4 effectively reversed this chemoresistance phenotype. In translational validation, combined pharmacological inhibition of the PD-L1/ITGB4 axis with sorafenib synergistically suppressed tumor progression in vivo, achieving >60% greater volume reduction compared to monotherapies.</p><p><strong>Conclusion: </strong>The PD-L1/ITGB4 axis drives sorafenib resistance via FAK/AKT/mTOR hyperactivation. Dual targeting of PD-L1/ITGB4 enhances sorafenib efficacy, revealing a tumor-intrinsic mechanism and proposing a novel combinatorial strategy for HCC.</p>","PeriodicalId":30986,"journal":{"name":"ImmunoTargets and Therapy","volume":"14 ","pages":"815-830"},"PeriodicalIF":4.4,"publicationDate":"2025-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12358154/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144875567","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":"Predicting ICU Admission in Patients with Autoimmune Glial Fibrillary Acidic Protein Astrocytopathy.","authors":"Xiao-Hong Su, Wei-Peng Li, Xiao-Feng Xu, Xiao-Ling Su, Jia Liu, Shi-Yuan Feng, Jun-Yu Liu, Rui-Qi Dong, Iok Keng Ngai, Lu Yang, Li Xu, Zhe-Qi Li, Dong-Cheng Li, Ying Jiang, Fu-Hua Peng","doi":"10.2147/ITT.S522190","DOIUrl":"10.2147/ITT.S522190","url":null,"abstract":"<p><strong>Introduction: </strong>Autoimmune glial fibrillary acidic protein astrocytopathy (A-GFAP-A) is an increasingly recognized neurological disorder with significant clinical management challenges, particularly in predicting the need for intensive care unit (ICU) admission. This study aimed to develop and validate predictive models to identify A-GFAP-A patients at increased risk for ICU admission.</p><p><strong>Methods: </strong>We retrospectively analyzed 107 patients (January 2021 - August 2024), randomly assigned to training and validation cohorts (7:3). Variable selection for model development was performed using random forest, least absolute shrinkage and selection operator (LASSO), and extreme gradient boosting (XGBoost). Logistic regression was used to construct a nomogram, and a decision tree was developed to facilitate rapid clinical decision-making. Model performance was assessed by area under the curve (AUC), calibration plots, and decision curve analysis (DCA).</p><p><strong>Results: </strong>Four key predictors of ICU admission were identified: Glasgow Coma Scale (GCS) score at admission, seizures, maximum body temperature, and C-reactive protein (CRP) levels. The nomogram demonstrated excellent predictive accuracy with AUCs of 0.923 (95% CI, 0.858-0.987) in training cohort, 0.922 (95% CI, 0.836-1.000) in validation cohort, and 0.93 (95% CI, 0.883-0.972) in bootstrap validation. The model showed excellent calibration, and DCA confirmed its clinical utility. The decision tree identified GCS <15, seizures, and temperature >39°C as the most relevant indicators for high-risk stratification.</p><p><strong>Discussion: </strong>This study presents the first validated nomogram and decision tree for ICU admission risk in A-GFAP-A, based on the largest reported cohort to date, providing a valuable tool for clinical decision-making and resource optimization.</p>","PeriodicalId":30986,"journal":{"name":"ImmunoTargets and Therapy","volume":"14 ","pages":"799-814"},"PeriodicalIF":4.4,"publicationDate":"2025-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12341804/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144838032","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":"Hepatic Metabolic Signature and Its Association with the Response to Immunotherapy in Hepatocellular Carcinoma.","authors":"Hyewon Park, Sowon Park, Kena Park, Sun Young Yim, Ju-Seog Lee, Sung Hwan Lee","doi":"10.2147/ITT.S491464","DOIUrl":"10.2147/ITT.S491464","url":null,"abstract":"<p><strong>Introduction: </strong>Increased metabolic activity is frequently observed in hepatocellular carcinoma (HCC). However, the impact of this increased metabolic activity on the efficacy of current treatments, such as the combination immunotherapy using atezolizumab and bevacizumab for HCC, remains unknown.</p><p><strong>Methods: </strong>Gene expression data from mouse livers representing hepatic metabolic activity and HCC patient tumor tissues were used to identify a transcriptomic signature for high metabolic activity in HCC tumors. The hepatic metabolic signature (HMS) was used to categorize HCC patients treated with atezolizumab plus bevacizumab or sorafenib from the IMbrave150 clinical trial into high-or low-metabolic groups, using multiple statistical approaches to evaluate the clinical relevance of the signature.</p><p><strong>Results: </strong>The study uncovered a robust association between high HMS and poor overall survival in HCC patients across multiple independent cohorts. Notably, high HMS patients in IMbrave150 did not show significant benefit of the atezolizumab-bevacizumab treatment in terms of overall survival or progression-free survival compared to sorafenib monotherapy. Conversely, low HMS patients demonstrated superior overall and progression-free survival outcomes with the combination regimen relative to sorafenib alone. Furthermore, an association between high HMS and features of hepatic stem cells and increased genomic instability was identified.</p><p><strong>Conclusion: </strong>This study provides compelling evidence that the HMS could be a predictive biomarker to identify potential HCC patients with therapeutic benefits from combination immunotherapy with atezolizumab and bevacizumab. Leveraging such predictive metabolic biomarkers may pave the way for tailored, precision medicine strategies that maximize therapeutic responses and improve outcomes for HCC patients.</p>","PeriodicalId":30986,"journal":{"name":"ImmunoTargets and Therapy","volume":"14 ","pages":"787-798"},"PeriodicalIF":4.4,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12296714/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144733556","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":"Mitophagy: A Potential Therapeutic Target for Tuberculosis Immunotherapy.","authors":"Siyu Gao, Zeliang Yang, Jiajia Yu, Fuzhen Zhang, Shenjie Tang, Yu Pang","doi":"10.2147/ITT.S518628","DOIUrl":"10.2147/ITT.S518628","url":null,"abstract":"<p><p>Mitophagy serves as a cytoprotective mechanism that is essential for eliminating dysfunctional or superfluous mitochondria, thereby fine-tuning mitochondrial quantity and maintaining cellular homeostasis. Recent studies underscore the critical role of mitophagy in determining the fate and function of host cells infected by <i>Mycobacterium tuberculosis</i>. The successful pathogen strategically integrates into the host's mitochondrial network, manipulating processes such as apoptosis, metabolic reprogramming, mitochondrial fusion and fission, and reactive oxygen species production. Therefore, understanding those mechanisms is critical for the advancements of host-directed therapies against tuberculosis. This study offers a comprehensive overview of the interplay between <i>Mycobacterium tuberculosis</i> and mitophagy, emphasizing the associated signaling pathways and potential therapeutic targets involved in mitophagy in <i>Mycobacterium tuberculosis</i> infection. Activating mitophagy in infected host cells represents a promising avenue for improving therapeutic outcomes against tuberculosis. This review aims to summarize potential research direction for agents targeting induction of mitophagy. Notably, evidence suggests that BNIP3/NIX-mediated mitophagy may serve as a potential therapeutic target.</p>","PeriodicalId":30986,"journal":{"name":"ImmunoTargets and Therapy","volume":"14 ","pages":"773-786"},"PeriodicalIF":4.4,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12301142/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144733557","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}