ImmunoTargets and Therapy最新文献

{"title":"Upregulated <i>BLM</i> and <i>RECQL4</i> in Osteosarcoma: Association with Poor Prognosis, Immune Cell Infiltration, and Inhibitory Effects of Sphingosine Kinase 1 Inhibitor II/Pilaralisib.","authors":"Jv Chen, Yongli Situ, Jie Cai, Wenyu Liao, Dongbo Jiang, Chengshuo Huang, Jinchang Zheng, Lijiao Peng, Hao Lin","doi":"10.2147/ITT.S569823","DOIUrl":"10.2147/ITT.S569823","url":null,"abstract":"<p><strong>Purpose: </strong><i>BLM</i> and <i>RECQL4</i>, key RecQ helicases and \"genome guardians\", maintain genomic stability. Their abnormal function/dysregulated expression is linked to tumorigenesis, but their roles in osteosarcoma (OS) remain unclear.</p><p><strong>Patients and methods: </strong>Comprehensive bioinformatic analyses (multiple public databases) assess OS-related expression, gene networks, prognosis, targets, and drugs. Cellular experiments verified the effects of these compounds on 143B cell proliferation, migration, and invasion.</p><p><strong>Results: </strong><i>BLM</i> and <i>RECQL4</i> were significantly upregulated in OS tissues compared to normal tissues, correlating with a poor prognosis. Among the 153 patients with OS, 9% and 7% had altered <i>BLM</i> and <i>RECQL4</i> expression, respectively. Abnormal methylation of <i>BLM</i> and <i>RECQL4</i> may affect OS. <i>BLM, RECQL4</i>, and their altered neighboring genes (ANGs) form interaction networks that regulate tumor metabolism, proliferation, migration, and apoptosis. Their miRNA and kinase targets in OS were also identified. <i>BLM</i> and <i>RECQL4</i> expression was negatively correlated with OS immune cell infiltration. In addition, anti-PD-1/CTLA-4/PD-L1 therapy, Sphingosine kinase 1 inhibitor II, and pilaralisib inhibited OS cell viability (by downregulating <i>BLM</i> or <i>RECQL4</i>) and the proliferation, migration, and invasion of 143B cells. Knockdown of <i>BLM</i> or <i>RECQL4</i> suppressed the migration and invasion of 143B cells.</p><p><strong>Conclusion: </strong><i>BLM</i> and <i>RECQL4</i> are promising prognostic biomarkers and therapeutic targets for OS.</p>","PeriodicalId":30986,"journal":{"name":"ImmunoTargets and Therapy","volume":"15 ","pages":"569823"},"PeriodicalIF":4.1,"publicationDate":"2026-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13006184/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147515415","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":"A Retrospective Study on the Clinical Characteristics and Management of Immune-Related Adverse Events in Gynecologic Cancer Patients Treated with Immune Checkpoint Inhibitors.","authors":"Yu Xia, Song Gao, Qianxue Wei, Wen Gu, Xiuqin Li, Hui Qu","doi":"10.2147/ITT.S566542","DOIUrl":"10.2147/ITT.S566542","url":null,"abstract":"<p><strong>Purpose: </strong>This study aimed to characterize the clinical profile, risk factors, and management of immune-related adverse events (irAEs) in patients with gynecologic cancers treated with immune checkpoint inhibitors (ICIs).</p><p><strong>Methods: </strong>In this single-center retrospective study, we analyzed data from 626 gynecologic cancer patients who received ICIs at our institution between January 2019 and July 2024. Data on the occurrence, grading, organ involvement, management, and potential risk factors of irAEs were collected and analyzed using binary logistic regression.</p><p><strong>Results: </strong>Of the 626 patients, 136 (21.7%) developed irAEs. The most commonly affected systems were endocrine (11.7%), cardiac (3.2%), and skin (2.6%). The incidence of grade 1-2 and grade 3-4 irAEs was 17.7% and 3.99%, respectively. The median time to irAE onset was 9 weeks (after 3 treatment cycles). Binary logistic regression analysis revealed that anti-PD-1/CTLA-4 bispecific antibody was a significant risk factor for irAEs (OR = 2.874, p < 0.0001), whereas a higher number of treatment cycles and combination immunotherapy regimens were protective factors. Most irAEs were managed with intravenous methylprednisolone daily. No irAE-related deaths occurred.</p><p><strong>Conclusion: </strong>In this cohort of gynecologic cancer patients receiving ICIs, our findings suggest a considerable prevalence of endocrine and cardiac irAEs and identify several treatment-related factors associated with irAE risk. The results may underscore the potential importance of timely glucocorticoid initiation, and could support the consideration of empirical steroid therapy in critically ill patients when diagnostic confirmation is difficult. These findings point to the potential importance of organ-specific monitoring and provide insights that could inform the development of management strategies for this population.</p>","PeriodicalId":30986,"journal":{"name":"ImmunoTargets and Therapy","volume":"15 ","pages":"566542"},"PeriodicalIF":4.1,"publicationDate":"2026-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13039660/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147610198","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":"Macrophage-Derived Transcriptional Signatures Predict Prognosis and Drug Sensitivity in Thyroid Cancer: Integrative Analysis and Experimental Validation of SMYD3.","authors":"Sufang Xu, Xin Zhang, Jingru Sun, Man Qin, Huarong Du, Bing Luo","doi":"10.2147/ITT.S565624","DOIUrl":"10.2147/ITT.S565624","url":null,"abstract":"<p><strong>Background: </strong>Thyroid cancer is the most common malignancy of the endocrine system. Tumor-associated macrophages (TAMs) play a pivotal role in modulating the tumor microenvironment and promoting tumor progression. However, the prognostic implications of macrophage heterogeneity in thyroid cancer remain unclear.</p><p><strong>Methods: </strong>Single-cell RNA-seq analysis was conducted to identify tumor-enriched macrophage subpopulations and hdWGCNA was used to define related gene modules. A prognostic model was built using 117 machine learning algorithm combinations and validated by Kaplan-Meier analysis. A nomogram combining clinical features and risk scores was established. Genomic alterations, immune profiles, and treatment responses were compared between risk groups using TCGA and GDSC2 datasets. In vitro experiments were performed to validate the role of SMYD3 in tumor progression and drug sensitivity.</p><p><strong>Results: </strong>Single-cell analysis identified a tumor-enriched macrophage subset with distinct functional states. hdWGCNA revealed macrophage-related gene modules linked to poor prognosis, and a machine learning-based model effectively stratified patient risk. High-risk patients had worse survival, older age, advanced stage, and lower BRAF mutation frequency but more diverse oncogenic alterations. They also showed enhanced T-cell exclusion and altered immune infiltration. Drug prediction analysis indicated greater sensitivity to Rapamycin, BDP-00009066, AZD5363_1916, and Cediranib_1922 in the high-risk group. Functional assays confirmed that SMYD3 knockdown suppressed proliferation and migration, and reduced sensitivity to AZD5363_1916, highlighting its role in modulating therapeutic response.</p><p><strong>Conclusion: </strong>This study identifies a tumor-enriched macrophage subpopulation with prognostic relevance and develops a robust machine learning-based model for risk stratification in thyroid cancer. SMYD3 is implicated in both tumor progression and drug sensitivity, offering a potential biomarker for precision treatment strategies.</p>","PeriodicalId":30986,"journal":{"name":"ImmunoTargets and Therapy","volume":"15 ","pages":"565624"},"PeriodicalIF":4.1,"publicationDate":"2026-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12998577/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147487604","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":"Induction Chemotherapy Followed by Immunotherapy Increases Pathological Complete Response Rate in dMMR/MSI-H Gastric Cancer: A Retrospective Cohort Study.","authors":"Hong Zeng, Yingying Wu, Ziwei Zhang, Jingdong Liu, Jie Sun, Xinyou Liu, Yuan Gu, Mengxin Tian, Weidong Chen, Zhenbin Shen, Kuntang Shen, Chen Xu, Xuefei Wang, Zhaoqing Tang, Yihong Sun","doi":"10.2147/ITT.S564230","DOIUrl":"10.2147/ITT.S564230","url":null,"abstract":"<p><strong>Background: </strong>Immune checkpoint inhibitor (ICI)-based strategies have become a consensus in the preoperative treatment of mismatch repair-deficient (dMMR)/microsatellite instability-high (MSI-H) gastric cancer (GC). However, the necessity and optimal strategy of combining ICIs with chemotherapy remain uncertain.</p><p><strong>Methods: </strong>This retrospective study aimed to evaluate the efficacy of different preoperative chemo-immunotherapy combinations in patients with dMMR/MSI-H GC. According to their therapeutic regimens, patients were divided into three cohorts: ICI-alone cohort; immunotherapy with induction chemotherapy (IC) cohort (ICI + IC): 1-2 cycles of IC followed by ICI; concurrent chemo-immunotherapy cohort (ICI + chemo): ICI combined with chemotherapy throughout the entire preoperative treatment. The pathological complete response (pCR) rate and major pathological response (MPR) rate were analyzed. Peripheral blood parameters before and after preoperative treatment were analyzed.</p><p><strong>Results: </strong>A total of 45 patients with locally advanced or oligometastatic dMMR/MSI-H GC were included. Baseline characteristics were well balanced among the three cohorts. The pCR rates were 18.2% (95% CI, 2.3-51.8%) in the ICI-alone cohort, 85.7% (95% CI, 42.1-99.6%) in the ICI + IC cohort, and 37.0% (95% CI, 19.4-57.6%) in the ICI + chemo cohort. Notably, the ICI + IC cohort showed a significantly higher pCR rate than the other two cohorts (p=0.015). The MPR rates were 54.5%, 85.7%, and 48.1% in the three cohorts, respectively, with no statistical significance. After preoperative treatment, monocyte-to-lymphocyte ratio exhibited an upward trend in the ICI + IC (p=0.100) and ICI + chemo (p=0.058) cohorts, indicating enhanced antigen presentation activity and immune activation.</p><p><strong>Conclusion: </strong>A preoperative strategy of IC followed by ICIs significantly increased pCR rate compared to ICI monotherapy or concurrent chemo-immunotherapy, suggesting a more effective strategy for patients with resectable dMMR/MSI-H GC. Given its retrospective design, small sample size, and lack of safety data, this study warrants validation in prospective clinical trials.</p>","PeriodicalId":30986,"journal":{"name":"ImmunoTargets and Therapy","volume":"15 ","pages":"564230"},"PeriodicalIF":4.1,"publicationDate":"2026-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12998556/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147487655","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":"The Value of the Preoperative Hematological Inflammatory Markers for Predicting Lymphovascular Invasion in Gastric Cancer.","authors":"Cong Li, Yanyan Wang, Shumei Liang, Huina Shi, Xuelian Mao, Xiao Wang, Dongping Mo","doi":"10.2147/ITT.S564201","DOIUrl":"10.2147/ITT.S564201","url":null,"abstract":"<p><strong>Background: </strong>Gastric cancer (GC) is a prevalent malignant tumor of the digestive system, with high morbidity and mortality. Lymphovascular invasion (LVI) is a risk factor for recurrence and metastasis of GC and an independent predictor of poor postoperative prognosis in GC patients. Accumulating evidence suggests that blood-based inflammatory indicators are linked with the pathogenesis of GC. The study delves into hematological inflammatory markers to explore their potential applications in preoperative LVI in GC.</p><p><strong>Methods: </strong>We retrospectively collected and analyzed data from inpatients diagnosed GC at our hospital from December 2020 to October 2024, with LVI confirmed by pathological examination after surgery. Preoperative hematological inflammatory indicators were calculated from peripheral blood samples. Lasso logistic regression and multivariate logistic regression analyses were utilized to verify independent risk factors for LVI-positive GC patients and constructed the nomogram model. The correlation between hematological inflammatory indicators and clinical TNM staging was assessed through Spearman's analysis.</p><p><strong>Results: </strong>In the study, 624 patients were pathological diagnosed with LVI-positive. The variables screened by Lasso logistic regression including CA199, PLR, SII, PNI, cT staging, and cN staging. Multivariate logistic regression analysis confirmed that CA199 (OR = 1.349, 95% CI: 1.016-1.790), PLR (OR = 1.396, 95% CI: 1.005-1.939), PNI (OR = 0.706, 95% CI: 0.515-0.968), cT staging (OR = 1.737, 95% CI: 1.511-1.996) and cN staging (OR = 2.272, 95% CI: 1.975-2.613) were independent risk factors of LVI-positive. PLR was positively correlated with cT and cN staging, while PNI was negatively correlated with both. The C-statistic of the nomogram model was 0.845, with a sensitivity of 86.86% and a specificity of 69.90%.</p><p><strong>Conclusion: </strong>We provided a new perspective on the clinical application of preoperative hematological inflammatory markers in the auxiliary diagnosis of LVI-positive in GC patients.</p>","PeriodicalId":30986,"journal":{"name":"ImmunoTargets and Therapy","volume":"15 ","pages":"564201"},"PeriodicalIF":4.1,"publicationDate":"2026-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12998561/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147487658","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":"Identification of Comprehensive Landscape of Peripheral Immunity and Chemokine-Related Genes in Amyotrophic Lateral Sclerosis.","authors":"Xinyu Yang, Sen Huang, Yuxin Wang, Jing Yuan, Xiaoli Yao","doi":"10.2147/ITT.S566733","DOIUrl":"10.2147/ITT.S566733","url":null,"abstract":"<p><strong>Purpose: </strong>Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease. Progressive loss of motor neuron function and disruption of the blood-brain barrier are key features of ALS. Under the influence of chemokines, peripheral immune cells migrate into the central nervous system, thereby affecting the neuronal microenvironment. The aim of this study is to classify ALS based on the immune characteristics of peripheral blood in patients with the disease, and to construct prognostic models.</p><p><strong>Patients and methods: </strong>A total of 397 ALS patients and 645 healthy controls (GSE112676 and GSE112680) were included. ALS chemotactic subtypes were constructed based on differentially expressed genes of chemokine and chemokine receptors (CCRs). The Cibersort algorithm was used to investigate the abundance of immune cells in peripheral blood. Univariate Cox regression analysis was performed to screen for CCRs genes, clinical characteristics, and immune cells associated with prognosis. Prognostic models were constructed based on these variables. Finally, external validation was conducted using samples from ALS patients diagnosed at the First Affiliated Hospital of Sun Yat-sen University.</p><p><strong>Results: </strong>There were significant differences in the abundance of peripheral immune cells between ALS patients and healthy controls. 17 CCRs genes were identified as differentially expressed. CCL23, CCR8, CXCR4, site of onset, age of onset, and \"CD4 naive T cells\" were demonstrated to be significantly correlated with survival time. Two chemotactic subtypes were established. Eight prognostic models could distinguish between high-risk and low-risk ALS patients. At year five, the areas under the receiver operating characteristic curves for the PlsRcox, Coxboost, and Xgboost algorithms were 0.747, 0.733, and 0.728, respectively. External test sets successfully validated these results.</p><p><strong>Conclusion: </strong>ALS patients exhibit peripheral immune abnormalities. Peripheral immune status could be used to distinguish ALS subtypes and construct prognostic models. Understanding peripheral immune changes in ALS patients may inform potential immunotherapies.</p>","PeriodicalId":30986,"journal":{"name":"ImmunoTargets and Therapy","volume":"15 ","pages":"566733"},"PeriodicalIF":4.1,"publicationDate":"2026-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12794310/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145967205","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":"Effectiveness and Safety of Eculizumab in Highly Active AChR+gMG and Its Therapeutic Response in Different Subtypes of gMG.","authors":"Tianying Ma, Yanan Liu, Ying Zhu, Yan Gao, Xue Wang, Yong Liang, Benqiao Wang, Ruixia Zhu","doi":"10.2147/ITT.S559497","DOIUrl":"10.2147/ITT.S559497","url":null,"abstract":"<p><strong>Background: </strong>Eculizumab had been approved for anti-acetylcholine receptor antibody-positive (AChR+) refractory myasthenia gravis (MG), but its effect on the broader group of highly active generalized myasthenia gravis (gMG) in clinical practice has not been fully uncovered.</p><p><strong>Methods: </strong>We conduct a retrospective multi-center cohort study with prospectively collected data to explore the effectiveness and safety of eculizumab in highly active patients in clinical practice.</p><p><strong>Results: </strong>Thirty-three patients from 4 research centers were included in our study treated with eculizumab. This study contains 1 early onset MG (EOMG), 13 late-onset MG (LOMG), and 19 thymoma-associated MG (TAMG) patients. At week 12, the mean Myasthenia Gravis Activities of Daily Living (MG-ADL) score decreased by 7.97 ± 3.96 points and Quantitative Myasthenia Gravis (QMG) score decreased by 12.88±5.82 points,13 (40%) patients achieved minimal symptom expression (MSE) and 78.7% patients were ADL responders (the improvement of MG-ADL score ≥3 points and lasted for at least 4weeks). The improvement was sustained for 24 weeks. Overall, four patients had experienced myasthenic crisis (MC), and the time to wean from mechanical ventilation (MV) was 6.33±3.21 days. In muscle subdomains analysis, QMG score decreased more obviously in the ocular group (66%) and bulbar group (49%) than in other muscle groups at week 4. Moreover, subgroup analysis showed that the TAMG and LOMG groups exhibited a similar degree of therapeutic effect in symptom control and ADL response. The mean prednisone dose was reduced by 12.84±20.36 mg/day at week 24. Patients in our study showed well tolerance to eculizumab, and none of them experienced meningococcal infections.</p><p><strong>Conclusion: </strong>Our study confirmed the safety and effectiveness of eculizumab in highly active gMG patients with reducing steroid dose. TAMG and MC may be suitable indications for treatment with eculizumab. All the muscle groups achieved improvements, especially for the extraocular muscles.</p>","PeriodicalId":30986,"journal":{"name":"ImmunoTargets and Therapy","volume":"15 ","pages":"559497"},"PeriodicalIF":4.1,"publicationDate":"2026-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12990246/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147475394","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":"Risk and Management of Bowel Obstruction in Colorectal Cancer Patients Undergoing Immunotherapy: A Cross-Sectional Multicenter Study.","authors":"Zhi-Gang Hong, Binyi Xiao, Muxu Zheng, Wanjun Yang, Liangjun Zhu, Guodong Liang, Yuhao Luo, Jinghua Tang, Weijian Mei, Jie-Hai Yu, Zhenlin Hou, Xiaojun Wu, Peirong Ding, Wu Jiang","doi":"10.2147/ITT.S563431","DOIUrl":"10.2147/ITT.S563431","url":null,"abstract":"<p><strong>Background: </strong>Despite the remarkable efficacy of immunotherapy for mismatch repair-deficient (dMMR)/microsatellite instability-high (MSI-H) colorectal cancer (CRC), patients may still develop bowel obstruction during tumor regression.</p><p><strong>Methods: </strong>The study cohort included CRC patients who received immunotherapy at four medical centers. Bowel obstruction risk was assessed, and clinicopathological and molecular features were recorded. A Bayesian model was used to identify risk factors.</p><p><strong>Results: </strong>A total of 214 patients were reviewed, with 196 patients meeting the eligibility criteria. Bowel obstruction occurred in 22 patients (10.3%) during immunotherapy. Obstruction was more commonly observed in patients with T4 stage tumors (<i>P</i>= 0.008), metastatic disease (<i>P</i> < 0.001), and an impassable lumen on baseline endoscopy (<i>P</i> = 0.022). Multivariable analysis revealed that T4 tumor was identified as an independent risk factor (odds ratios: 8.36, 95% confidence interval: 1.20-80.34). Among responders with obstructions, the median time to response was 6.1 weeks (interquartile range [IQR]: 5.5-10.7), the best response was 9.9 weeks (IQR: 5.6-23.6), and obstruction occurred at 6.6 weeks (IQR: 5.3-9.2). Notably, 42.9% (6/14) of the patients developed obstructions after laxative use during endoscopy. Four patients (18.2%) required surgery. Three (21.4%) patients in supportive therapy experienced recurrent obstructions. Four patients underwent endoscopic treatment (two stents, two balloon dilatations), all with symptom relief.</p><p><strong>Conclusion: </strong>Bowel obstruction was common in CRC patients receiving immunotherapy. This risk may be suggested by two clinical features at baseline. Obstructions often occurred after the initial response but before the best overall response. Early detection and proper management may help to prevent or reduce obstructions.</p>","PeriodicalId":30986,"journal":{"name":"ImmunoTargets and Therapy","volume":"15 ","pages":"563431"},"PeriodicalIF":4.1,"publicationDate":"2026-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13038036/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147595015","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":"Flow Cytometric Profiling of Peripheral Immune Checkpoints Predicts Prognosis and Reveals PD-1/Treg/IL-10 Crosstalk in B-Cell Lymphoma.","authors":"Bing Pan, Sijia Li, Ruyu Ye, Jie Zhu, Yawei Tang, Li Li","doi":"10.2147/ITT.S561672","DOIUrl":"10.2147/ITT.S561672","url":null,"abstract":"<p><strong>Background: </strong>The clinical significance and mechanistic role of immune checkpoints (ICs) in B-cell lymphoma remain underexplored. This study investigates peripheral IC expression as prognostic biomarkers and their interaction with Tregs and IL-10.</p><p><strong>Methods: </strong>Peripheral blood from 140 B-cell lymphoma patients was analyzed using flow cytometry (PD-1, CTLA-4, LAG-3, TIM-3 on CD4⁺/CD8⁺ T cells) and ELISA. Comparisons were made across disease aggressiveness, extranodal involvement, and treatment response (complete remission [CR] vs relapse/progression [R/P]).</p><p><strong>Results: </strong>Aggressive lymphomas and cases with multiple extranodal sites showed significantly elevated IC expression (all p < 0.05). R/P patients demonstrated markedly higher PD-1 expression (CD4⁺: 26.1% vs 8.2%; CD8⁺: 25.2% vs 7.1%; p < 0.001) and elevated CTLA-4, LAG-3, TIM-3 versus CR patients. PD-1 and CTLA-4 showed significant prognostic value (AUC > 0.7), unlike LAG-3/TIM-3. R/P patients had increased Treg proportions (7.84% vs 3.58%, P<0.0001) and IL-10 levels (10.5 vs 5.44 pg/mL, p < 0.0001). PD-1 on CD4⁺ T cells correlated positively with Treg frequency (r = 0.539, p < 0.0001) and IL-10 levels (r = 0.457, p < 0.0001).</p><p><strong>Conclusion: </strong>Peripheral T-cell ICs, particularly PD-1 and CTLA-4, are significant prognostic biomarkers in B-cell lymphoma. The correlation between PD-1⁺ CD4⁺ T cells, Treg expansion, and IL-10 elevation is consistent with a mechanism whereby PD-1 signaling may contribute to immunosuppression through Treg differentiation and JAK2/STAT3 pathway activation, providing insights for therapeutic targeting.</p>","PeriodicalId":30986,"journal":{"name":"ImmunoTargets and Therapy","volume":"14 ","pages":"1555-1568"},"PeriodicalIF":4.4,"publicationDate":"2025-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12766162/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145913247","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":"TLR9: A Double-Dealing Toll-Like Receptor.","authors":"Megan Nielsen, Daisuke Nishizaki, Shumei Kato, Razelle Kurzrock","doi":"10.2147/ITT.S563765","DOIUrl":"10.2147/ITT.S563765","url":null,"abstract":"<p><p>In 2011, the Nobel Prize was awarded for the discovery of Toll-like receptors (TLRs) and their critical role in immunity. TLR9 is a key pattern recognition receptor that detects unmethylated cytosine-phosphate-guanine (CpG) DNA motifs, triggering innate and adaptive immune responses against pathogens and damaged host cells. Upon activation, TLR9 triggers signaling cascades that drive NF-κB, STAT3, and MAPK pathways, modulating inflammatory responses, cellular survival mechanisms, and immune regulation. While TLR9 activation is essential for immune defense, TLR9 acts as a double-dealing TLR in multiple pathologies, including cancer, autoimmunity, and chronic inflammatory disease. In cancer biology, TLR9 exhibits context-dependent roles, acting as a driver of tumorigenesis, a suppressor of tumor growth, and a regulator of immune responses, depending on the tumor type, signaling pathway, and microenvironment. It promotes tumorigenesis in leukemias, gliomas, and cancers of the prostate, bone, lung, and gastrointestinal tract, yet displays tumor-suppressive effects in triple-negative breast cancer, renal cell carcinoma, and virally-associated malignancies, through a variety of mechanisms. Clinically, synthetic CpG oligodeoxynucleotides (ODNs), which function as TLR9 agonists, have emerged as a promising approach in cancer immunotherapy, particularly in combination with other potent anticancer therapies. However, the dual nature of TLR9 signaling poses challenges for therapeutic applications. Its context-dependent effects contribute to inconsistent clinical outcomes and raise concerns about safety and toxicity. This review examines the immunologic function and signaling mechanisms of TLR9, with a focus on its complex, context-specific, and \"double-dealing\" roles in cancer pathogenesis and therapy.</p>","PeriodicalId":30986,"journal":{"name":"ImmunoTargets and Therapy","volume":"14 ","pages":"1531-1554"},"PeriodicalIF":4.4,"publicationDate":"2025-12-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12764342/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145901193","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}