ImmunoTargets and Therapy最新文献

筛选
英文 中文
Identification of CRTH2 as a New PPARγ-Target Gene in T Cells Suggested CRTH2 Dependent Conversion of Th2 Cells as Therapeutic Concept in COVID-19 Infection. 鉴定 CRTH2 是 T 细胞中新的 PPARγ 靶基因,建议将 CRTH2 依赖性 Th2 细胞转化作为 COVID-19 感染的治疗概念。
IF 6.2
ImmunoTargets and Therapy Pub Date : 2024-11-02 eCollection Date: 2024-01-01 DOI: 10.2147/ITT.S463601
Antonia Becker, Karoline Röhrich, Amanda Leske, Ulrike Heinicke, Tilo Knape, Aimo Kannt, Verena Trümper, Kai Sohn, Annett Wilken-Schmitz, Holger Neb, Elisabeth H Adam, Volker Laux, Michael J Parnham, Valerie Onasch, Andreas Weigert, Kai Zacharowski, Andreas von Knethen
{"title":"Identification of CRTH2 as a New PPARγ-Target Gene in T Cells Suggested CRTH2 Dependent Conversion of T<sub>h</sub>2 Cells as Therapeutic Concept in COVID-19 Infection.","authors":"Antonia Becker, Karoline Röhrich, Amanda Leske, Ulrike Heinicke, Tilo Knape, Aimo Kannt, Verena Trümper, Kai Sohn, Annett Wilken-Schmitz, Holger Neb, Elisabeth H Adam, Volker Laux, Michael J Parnham, Valerie Onasch, Andreas Weigert, Kai Zacharowski, Andreas von Knethen","doi":"10.2147/ITT.S463601","DOIUrl":"10.2147/ITT.S463601","url":null,"abstract":"<p><strong>Background: </strong>COVID-19 is a serious viral infection, which is often associated with a lethal outcome. Therefore, understanding mechanisms, which affect the immune response during SARS-CoV2 infection, are important.</p><p><strong>Methods: </strong>To address this, we determined the number of T cells in peripheral blood derived from intensive care COVID-19 patients. Based on our previous studies, evaluating PPARγ-dependent T cell apoptosis in sepsis patients, we monitored PPARγ expression. We performed a next generation sequencing approach to identify putative PPARγ-target genes in Jurkat T cells and used a PPARγ transactivation assay in HEK293T cells. Finally, we translated these data to primary T cells derived from healthy donors.</p><p><strong>Results: </strong>A significantly reduced count of total CD3<sup>+</sup> T lymphocytes and the CD4<sup>+</sup> and CD8<sup>+</sup> subpopulations was observed. Also, the numbers of anti-inflammatory, resolutive T<sub>h</sub>2 cells and FoxP3-positive regulatory T cells (T<sub>reg</sub>) were decreased. We observed an augmented PPARγ expression in CD4<sup>+</sup> T cells of intensive care COVID-19 patients. Adapted from a next generation sequencing approach in Jurkat T cells, we found the chemoattractant receptor-homologous molecule expressed on T helper type 2 cells (CRTH2) as one gene regulated by PPARγ in T cells. This T<sub>h</sub>2 marker is a receptor for prostaglandin D and its metabolic degradation product 15-deoxy-∆12,14-prostaglandin J<sub>2</sub> (15d-PGJ<sub>2</sub>), an established endogenous PPARγ agonist. In line, we observed an increased PPARγ transactivation in response to 15d-PGJ<sub>2</sub> treatment in HEK293T cells overexpressing CRTH2. Translating these data to primary T cells, we found that T<sub>h</sub>2 differentiation was associated with an increased expression of CRTH2. Interestingly, these CRTH2<sup>+</sup> T cells were prone to apoptosis.</p><p><strong>Conclusion: </strong>These mechanistic data suggest an involvement of PPARγ in T<sub>h</sub>2 differentiation and T cell depletion in COVID-19 patients.</p>","PeriodicalId":30986,"journal":{"name":"ImmunoTargets and Therapy","volume":null,"pages":null},"PeriodicalIF":6.2,"publicationDate":"2024-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11539866/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142590673","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}
引用次数: 0
The Effect of Circulating Inflammatory Proteins on Endometriosis: A Mendelian Randomization Study. 循环炎症蛋白对子宫内膜异位症的影响:孟德尔随机研究
IF 6.2
ImmunoTargets and Therapy Pub Date : 2024-11-01 eCollection Date: 2024-01-01 DOI: 10.2147/ITT.S486139
Yunfang Wei, Xianlei Zhao, Linxia Li
{"title":"The Effect of Circulating Inflammatory Proteins on Endometriosis: A Mendelian Randomization Study.","authors":"Yunfang Wei, Xianlei Zhao, Linxia Li","doi":"10.2147/ITT.S486139","DOIUrl":"10.2147/ITT.S486139","url":null,"abstract":"<p><strong>Background: </strong>Endometriosis is a complex gynecological condition in which endometrial fragments are implanted outside the uterus, causing pain and infertility. Although immune mediators play a vital role in endometriosis, their exact etiology remains elusive. Using Mendelian randomization (MR), this study aimed to assess the causal relationship between inflammatory proteins and endometriosis.</p><p><strong>Methods: </strong>Genetic variants associated with inflammatory proteins were filtered from a genome-wide protein quantitative trait locus study under stringent thresholds. These variants were used as instrumental variables (IVs) to evaluate the causal effects of these inflammatory proteins on endometriosis. A two-sample MR analysis was performed with endometriosis from the UK Biobank as the outcome, and a sensitivity analysis was performed to mitigate potential confounding factors. Analyses were replicated in an independent endometriosis cohort from the FinnGen, followed by a meta-analysis of MR results from both cohorts. Finally, we assessed the causality between inflammatory proteins and the endometriosis subtypes.</p><p><strong>Results: </strong>Independent MR analysis revealed that the genetically higher levels of CXCL5 were linked to a lower chance of having endometriosis. The causal link remained significant in the meta-analysis. Furthermore, the causality of CXCL5 expression has been identified in ovarian and pelvic peritoneal endometriosis.</p><p><strong>Conclusion: </strong>Our MR analysis indicated that CXCL5 was associated with a decreased risk of endometriosis, suggesting that CXCL5 might have a protective effect against endometriosis. This enhances our understanding of the involvement of chemokines in endometriosis pathology and provides insights for future studies to explore the detailed mechanisms underlying CXCL5 in endometriosis.</p>","PeriodicalId":30986,"journal":{"name":"ImmunoTargets and Therapy","volume":null,"pages":null},"PeriodicalIF":6.2,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11537175/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142584367","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}
引用次数: 0
Patients with Extensive-Stage Small Cell Lung Cancer Harboring Less Than 4 Metastatic Sites May Benefit from Immune Checkpoint Inhibitor Rechallenge by Reshaping Tumor Microenvironment. 转移部位少于4个的广泛期小细胞肺癌患者可通过重塑肿瘤微环境从免疫检查点抑制剂再挑战中获益
IF 6.2
ImmunoTargets and Therapy Pub Date : 2024-10-26 eCollection Date: 2024-01-01 DOI: 10.2147/ITT.S483093
Xiaoling Shang, Chenyue Zhang, Yuanyuan Lv, Xiaoxiao Zhang, Kaiyue Guo, Huijuan Li, Haiyong Wang
{"title":"Patients with Extensive-Stage Small Cell Lung Cancer Harboring Less Than 4 Metastatic Sites May Benefit from Immune Checkpoint Inhibitor Rechallenge by Reshaping Tumor Microenvironment.","authors":"Xiaoling Shang, Chenyue Zhang, Yuanyuan Lv, Xiaoxiao Zhang, Kaiyue Guo, Huijuan Li, Haiyong Wang","doi":"10.2147/ITT.S483093","DOIUrl":"10.2147/ITT.S483093","url":null,"abstract":"<p><strong>Background: </strong>Immune checkpoint inhibitors (ICIs) has prolonged survival in patients with extensive-stage small cell lung cancer (ES-SCLC) as first-line treatment. However, whether ICI rechallenge could bring survival benefit to patients with ES-SCLC following its failure as first-line treatment remains unknown. Therefore, we aim to address the issue and identify the cohort of patients that may derive such benefit.</p><p><strong>Methods: </strong>Patients with ES-SCLC from both the IMpower133 study and Shandong Cancer Hospital and Institute (shanzhong cohort) who failed first-line ICI were included. Kaplan Meier analysis was performed to compare overall survival (OS). Both univariate and multivariate Cox regression analyses were conducted to identify factors affecting survival. Tumor immune cell infiltration was evaluated by the CIBERSORT algorithm and detected by multiplex immunofluorescence (mIF).</p><p><strong>Results: </strong>A total of 125 ES-SCLC patients undergoing atezolizumab and 161 patients undergoing ICI as first-line treatment were recruited from IMpower133 and shanzhong cohort. Those receiving ICI rechallenge had a longer OS than those without in IMpower133 (<i>P</i> = 0.08) and shanzhong cohort (<i>P</i> = 0.013). In IMpower133 cohort, subgroup analyses found that patients with <4 metastatic sites derived more survival benefit from atezolizumab (<i>P</i> = 0.008). For patients with ES-SCLC harboring <4 metastatic sites, there was significant OS difference between atezolizumab versus non-atezolizumab as retreatment (<i>P</i> = 0.036). Moreover, for ES-SCLC patients with <4 metastatic sites, atezolizumab improved survival compared with non-atezolizumab (hazard ratio [HR]: 0.457; 95% CI: 0.256-0.817; <i>P</i> = 0.008). These findings were confirmed in shanzhong cohort. Those harboring <4 metastatic sites had fewer M2 macrophage and more CD4 naïve T cells infiltration, which was further confirmed by mIF of ES-SCLC samples from shanzhong cohort.</p><p><strong>Conclusion: </strong>Our study provides rationale for ICI rechallenge among ES-SCLC patients with <4 metastatic sites, suggesting beneficial outcome by reshaping TME.</p>","PeriodicalId":30986,"journal":{"name":"ImmunoTargets and Therapy","volume":null,"pages":null},"PeriodicalIF":6.2,"publicationDate":"2024-10-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11523948/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142547985","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}
引用次数: 0
The Efficacy and Safety of Bevacizumab Plus Anti-PD-1/PD-L1 Inhibitors in Combination with Hepatic Arterial Infusion Chemotherapy for Initially Unresectable Hepatocellular Carcinoma. 贝伐单抗加抗PD-1/PD-L1抑制剂联合肝动脉灌注化疗治疗最初无法切除的肝细胞癌的有效性和安全性。
IF 6.2
ImmunoTargets and Therapy Pub Date : 2024-10-26 eCollection Date: 2024-01-01 DOI: 10.2147/ITT.S478685
Xiang Tang, Jinbin Chen, Wei Peng, Zhoutian Yang, Li Hu, Zhiwei Ye, Yizhen Fu, Dandan Hu, Zhongguo Zhou, Minshan Chen, Yaojun Zhang, Jun-Cheng Wang
{"title":"The Efficacy and Safety of Bevacizumab Plus Anti-PD-1/PD-L1 Inhibitors in Combination with Hepatic Arterial Infusion Chemotherapy for Initially Unresectable Hepatocellular Carcinoma.","authors":"Xiang Tang, Jinbin Chen, Wei Peng, Zhoutian Yang, Li Hu, Zhiwei Ye, Yizhen Fu, Dandan Hu, Zhongguo Zhou, Minshan Chen, Yaojun Zhang, Jun-Cheng Wang","doi":"10.2147/ITT.S478685","DOIUrl":"10.2147/ITT.S478685","url":null,"abstract":"<p><strong>Objection: </strong>To report the efficacy and safety of triple combination therapy with bevacizumab plus anti-PD-1 (BP1) or anti-PD-L1 inhibitors (BPL) combined with hepatic arterial infusion chemotherapy (HAIC) as a first-line treatment for initially unresectable hepatocellular carcinoma (uHCC).</p><p><strong>Methods: </strong>In this retrospective study, patients with initially uHCC received either BP1-HAIC or BPL-HAIC as first-line treatment. The primary endpoint was progression-free survival (PFS); secondary endpoints included overall survival (OS), objective response rate (ORR) and disease control rate (DCR).</p><p><strong>Results: </strong>Between January 2020 and December 2022, a total of 136 patients with initially uHCC received triple combination therapy, with 76 in the BP1-HAIC group and 60 in the BPL-HAIC group. The median PFS for the entire cohort was 11.1 months (95% CI, 8.0-13.7 months), and the median OS was 22.4 months (95% CI, 21.3- not reached). Comparative analysis revealed no significant differences in PFS (HR, 0.91, <i>P</i> = 0.69) or OS (HR, 0.71, <i>P</i> = 0.31) between the BP1-HAIC and BPL-HAIC groups. The ORR was 46.3% per RECIST v1.1 and 66.9% per mRECIST, with a DCR of 83.1% under both criteria. Common adverse events (AEs) included hypoalbuminemia and elevated aspartate/alanine aminotransferase, with 5.1% (7/136) experienced upper gastrointestinal bleeding. Multivariate Cox analysis identified tumor number and BCLC stage as independent prognostic factors for OS, and tumor number for PFS.</p><p><strong>Conclusion: </strong>Triple combination therapy demonstrated significant therapeutic efficacy and tumor response in initially uHCC. No notable differences in outcomes were observed between the BP1-HAIC and BPL-HAIC groups. AEs were manageable in clinical practice.</p>","PeriodicalId":30986,"journal":{"name":"ImmunoTargets and Therapy","volume":null,"pages":null},"PeriodicalIF":6.2,"publicationDate":"2024-10-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11524013/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142547986","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}
引用次数: 0
Assessing the Prognostic Value of 13 Inflammation-Based Scores in Patients with Unresectable or Advanced Biliary Tract Carcinoma After Immunotherapy. 评估免疫疗法后不可切除或晚期胆管癌患者的 13 项炎症评分的预后价值
IF 6.2
ImmunoTargets and Therapy Pub Date : 2024-10-16 eCollection Date: 2024-01-01 DOI: 10.2147/ITT.S471502
Fang Wang, Chang Jiang, Wenzhuo He, Heping Li, Gui-Fang Guo, Lixia Xu
{"title":"Assessing the Prognostic Value of 13 Inflammation-Based Scores in Patients with Unresectable or Advanced Biliary Tract Carcinoma After Immunotherapy.","authors":"Fang Wang, Chang Jiang, Wenzhuo He, Heping Li, Gui-Fang Guo, Lixia Xu","doi":"10.2147/ITT.S471502","DOIUrl":"10.2147/ITT.S471502","url":null,"abstract":"<p><strong>Purpose: </strong>The response of patients with biliary tract carcinoma (BTC) to immunotherapy varies widely, and there is an urgent need for biological indicators. The predictive value of inflammation based score (IBS) for the efficacy of immunotherapy in patients with BTC remains unclear, as the evidence is inconsistent. This study aimed to comprehensively examine the predictive value of IBS in peripheral blood on the survival of BTC patients receiving immunotherapy.</p><p><strong>Patients and methods: </strong>We retrospectively assessed 118 patients with advanced BTC who received anti-PD-1 therapy in the first or second line in two medical centers. The Kaplan-Meier, time-dependent ROC, and Harrell's concordance index (C-index) were applied to analyze the predictive value of 13 reported peripheral blood IBS.</p><p><strong>Results: </strong>All 13 IBS were identified as significant prognostic factors for OS in univariate analysis. Pan-immune-inflammation value (PIV) (p=0.005), PILE (composed of PIV, lactate dehydrogenase and Eastern Cooperative Oncology Group performance status) (<i>p</i>=0.033), neutrophil-to-lymphocyte ratio (NLR) (<i>p</i>=0.003), platelet-to-lymphocyte ratio (PLR) (<i>p</i><0.001), lymphocyte-to-monocyte ratio (LMR) (<i>p</i>=0.006), systemic immune inflammation index (SII) (<i>p</i>=0.039), CRP-to-albumin ratio (CAR) (<i>p</i>=0.025), and Albumin-NLR (<i>p</i>=0.008) were identified as independent prognostic factors for OS in multivariate analysis. PIV and PILE scores were superior to other scores, according to time-dependent ROC curves, and their superiority became more pronounced after the 12-month time point. C-index analysis showed PIV (C-index 0.62, 95% CI: 0.55, 0.68) and PILE (C-index 0.62, 95% CI: 0.55, 0.70), both superior to other IBS.</p><p><strong>Conclusion: </strong>PIV and PILE scores are independent predictors of OS in patients with BTC after immunotherapy and are superior to other IBS. PIV and PILE may be able to help screen out patients with advanced BTC who are less likely to benefit from anti-PD-1 monotherapy. Due to the retrospective nature of this analysis, the predictive value of PIV and PILE require validation in further prospective studies.</p>","PeriodicalId":30986,"journal":{"name":"ImmunoTargets and Therapy","volume":null,"pages":null},"PeriodicalIF":6.2,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11491092/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142476416","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}
引用次数: 0
Harnessing Variability Signatures and Biological Noise May Enhance Immunotherapies' Efficacy and Act as Novel Biomarkers for Diagnosing and Monitoring Immune-Associated Disorders. 利用变异特征和生物噪音可提高免疫疗法的疗效,并可作为诊断和监测免疫相关疾病的新型生物标记物。
IF 6.2
ImmunoTargets and Therapy Pub Date : 2024-10-14 eCollection Date: 2024-01-01 DOI: 10.2147/ITT.S477841
Tal Sigawi, Adir Israeli, Yaron Ilan
{"title":"Harnessing Variability Signatures and Biological Noise May Enhance Immunotherapies' Efficacy and Act as Novel Biomarkers for Diagnosing and Monitoring Immune-Associated Disorders.","authors":"Tal Sigawi, Adir Israeli, Yaron Ilan","doi":"10.2147/ITT.S477841","DOIUrl":"10.2147/ITT.S477841","url":null,"abstract":"<p><p>Lack of response to immunotherapies poses a significant challenge in treating immune-mediated disorders and cancers. While the mechanisms associated with poor responsiveness are not well defined and change between and among subjects, the current methods for overcoming the loss of response are insufficient. The Constrained Disorder Principle (CDP) explains biological systems based on their inherent variability, bounded by dynamic boundaries that change in response to internal and external perturbations. Inter and intra-subject variability characterize the immune system, making it difficult to provide a single therapeutic regimen to all patients and even the same patients over time. The dynamicity of the immune variability is also a significant challenge for personalizing immunotherapies. The CDP-based second-generation artificial intelligence system is an outcome-based dynamic platform that incorporates personalized variability signatures into the therapeutic regimen and may provide methods for improving the response and overcoming the loss of response to treatments. The signatures of immune variability may also offer a method for identifying new biomarkers for early diagnosis, monitoring immune-related disorders, and evaluating the response to treatments.</p>","PeriodicalId":30986,"journal":{"name":"ImmunoTargets and Therapy","volume":null,"pages":null},"PeriodicalIF":6.2,"publicationDate":"2024-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11488351/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142476417","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}
引用次数: 0
A Self-Activating IL-15 Chimeric Cytokine Receptor to Empower Cancer Immunotherapy. 增强癌症免疫疗法的自激活 IL-15 嵌合细胞因子受体。
IF 6.2
ImmunoTargets and Therapy Pub Date : 2024-10-10 eCollection Date: 2024-01-01 DOI: 10.2147/ITT.S490498
Sumei Chen, Lingrong Yang, Bing Xia, Haitao Zhu, Zhenghao Piao, Youssef Jounaidi
{"title":"A Self-Activating IL-15 Chimeric Cytokine Receptor to Empower Cancer Immunotherapy.","authors":"Sumei Chen, Lingrong Yang, Bing Xia, Haitao Zhu, Zhenghao Piao, Youssef Jounaidi","doi":"10.2147/ITT.S490498","DOIUrl":"https://doi.org/10.2147/ITT.S490498","url":null,"abstract":"<p><strong>Background: </strong>Enhancing NK cells' antitumor activity requires sustained cytokine signaling. Interleukin-15 (IL-15) is a potent immunostimulatory cytokine used to armor CAR-NK and CAR-T cell immunotherapies. However, strategies to increase IL-15 expression and antitumor effect may trigger systemic toxicity with the potential to promote oncogenesis and autoimmune diseases.</p><p><strong>Methods: </strong>To overcome these limitations, we developed a new platform (IL15RB) whereby IL-15 with IL-2 signal peptide is tethered to its receptor, IL2Rβ.</p><p><strong>Results: </strong>NK92-expressing IL15RB (NK92<sup>IL15RB</sup>) cells expand indefinitely without exogenous cytokines and have significantly higher anticancer activity than NK-92 stimulated by IL-15, IL-2, or expressing tethered IL-2. NK92<sup>IL5RB</sup> showed resistance to irradiation and IL-4. However, TGFβ1 substantially reduced NK92<sup>IL5RB</sup> killing, suggesting the need to inhibit TGFβ1 in IL-15-mediated immunotherapies. IL15RB induced strong STAT3 but weaker STAT5 and STAT1 activation compared to IL-2. Chronic exposure of NK92<sup>IL15RB</sup> cells to cancer cells reduced STAT3 and STAT1 activation irreversibly, suggesting a role in exhaustion. Combination with CAR-CD19 enhanced NK92<sup>IL15RB</sup> antitumor activity against leukemia and increased its STAT5 activation. NK92<sup>IL15RB</sup> anti-tumors activity was further enhanced by combination with anti-PD1.</p><p><strong>Conclusion: </strong>Our data suggest that the tethering of IL-15 to its receptor IL2Rβ empowers NK cell cytolytic activity. Additionally, the tethering of IL-15 will prevent any systemic risk of toxicity.</p>","PeriodicalId":30986,"journal":{"name":"ImmunoTargets and Therapy","volume":null,"pages":null},"PeriodicalIF":6.2,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11472742/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142476415","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}
引用次数: 0
Clinical Outcomes of Patients Treated with Ribociclib in Combination with Aromatase Inhibitors or Fulvestrant for HR-Positive, HER2-Negative Metastatic Breast Cancer, Real-World Data from a Low-Resourced Country. Ribociclib联合芳香化酶抑制剂或氟维司群治疗HR阳性、HER2阴性转移性乳腺癌患者的临床疗效,来自资源匮乏国家的真实世界数据。
IF 6.2
ImmunoTargets and Therapy Pub Date : 2024-09-29 eCollection Date: 2024-01-01 DOI: 10.2147/ITT.S479153
Hikmat Abdel-Razeq, Baha Sharaf, Suhaib Khater, Huda Jafar Baidoun, Hira Bani Hani, Ayat Taqash, Osama El Khatib, Sarah Edaily, Mahmoud Abunasser, Faris Tamimi, Yosra Nabeel Al-Masri, Tamer Moh'd Waleed Al-Batsh, Anas Zayed, Tala Ghatasheh, Tala Radaideh
{"title":"Clinical Outcomes of Patients Treated with Ribociclib in Combination with Aromatase Inhibitors or Fulvestrant for HR-Positive, HER2-Negative Metastatic Breast Cancer, Real-World Data from a Low-Resourced Country.","authors":"Hikmat Abdel-Razeq, Baha Sharaf, Suhaib Khater, Huda Jafar Baidoun, Hira Bani Hani, Ayat Taqash, Osama El Khatib, Sarah Edaily, Mahmoud Abunasser, Faris Tamimi, Yosra Nabeel Al-Masri, Tamer Moh'd Waleed Al-Batsh, Anas Zayed, Tala Ghatasheh, Tala Radaideh","doi":"10.2147/ITT.S479153","DOIUrl":"10.2147/ITT.S479153","url":null,"abstract":"<p><strong>Background: </strong>Cyclin-dependent kinase (CDK) 4/6 inhibitors have revolutionized the treatment landscape of hormone receptor-positive (HR+) and human epidermal growth factor receptor 2-negative (HER2 -) metastatic breast cancer (MBC). Here, we present the real-world clinical outcomes and toxicity data of patients treated at a single cancer center.</p><p><strong>Methods: </strong>A retrospective analysis was conducted on patients with HR+/HER2- MBC treated with ribociclib plus endocrine therapy (ET). Outcomes measured included progression-free survival (PFS), overall survival (OS), and adverse events.</p><p><strong>Results: </strong>A total of 356 patients (median age 52, range 27-91 years) were enrolled, all with metastatic disease; 204 (57.5%) had de novo metastasis, and 183 (51.4%) had visceral metastasis. Ribociclib was combined with aromatase inhibitors in 321 patients (90.2%) and with fulvestrant in 35 patients (9.8%). Dose reduction was needed in 101 patients (28.4%), primarily due to neutropenia (21.3%) and abnormal liver enzymes (5.9%). After a median follow-up of 36.3 months, median PFS was 27.3 months (95% CI: 21.3-31.7). PFS was significantly better in patients receiving ribociclib as first-line therapy (32.1 months, 95% CI: 27.7-42.1, p < 0.0001) and those with non-visceral metastasis (38.6 months, 95% CI: 29.8-NR, p < 0.0001). Similarly, OS was significantly better in first-line treatment (48.6 months, 95% CI: 39.1-NR) and non-visceral metastasis cases (NR, 95% CI: 40.6-NR, p < 0.0001). No significant differences in 3-year PFS and OS were found between patients with and without dose reductions.</p><p><strong>Conclusion: </strong>In real-world settings, and away from the stringency of controlled clinical trials, endocrine therapy in combination with ribociclib in patients with HR-positive/HER2-negative MBC is an effective and well-tolerated therapy with a manageable toxicity profile and a low drug discontinuation rate. Dose reduction due to toxicity did not worsen the outcome.</p>","PeriodicalId":30986,"journal":{"name":"ImmunoTargets and Therapy","volume":null,"pages":null},"PeriodicalIF":6.2,"publicationDate":"2024-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11448467/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142373103","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}
引用次数: 0
EPS T14 from Bacillus licheniformis Prevents Infection of Human Nasal Epithelial Cells by Respiratory Viruses. 地衣芽孢杆菌的 EPS T14 可防止呼吸道病毒感染人鼻上皮细胞。
IF 6.2
ImmunoTargets and Therapy Pub Date : 2024-09-27 eCollection Date: 2024-01-01 DOI: 10.2147/ITT.S470319
Gaetana Pezzino, Alessia Calabrò, Fabiana Drommi, Stefania Campana, Riccardo Cavaliere, Irene Bonaccorsi, Paolo Carrega, Vincenzo Zammuto, Maria Giovanna Rizzo, Concetta Gugliandolo, Guido Ferlazzo, Claudia De Pasquale
{"title":"EPS T14 from <i>Bacillus licheniformis</i> Prevents Infection of Human Nasal Epithelial Cells by Respiratory Viruses.","authors":"Gaetana Pezzino, Alessia Calabrò, Fabiana Drommi, Stefania Campana, Riccardo Cavaliere, Irene Bonaccorsi, Paolo Carrega, Vincenzo Zammuto, Maria Giovanna Rizzo, Concetta Gugliandolo, Guido Ferlazzo, Claudia De Pasquale","doi":"10.2147/ITT.S470319","DOIUrl":"10.2147/ITT.S470319","url":null,"abstract":"<p><strong>Background: </strong>Respiratory viral infections are a leading cause of severe diseases and mortality; therefore, novel treatments effective for their prevention are highly requested. Here, we identified a broad-spectrum antiviral activity of a natural exopolysaccharide, EPS T14, purified from a marine thermotolerant strain of <i>Bacillus licheniformis</i> strain T14.</p><p><strong>Methods: </strong>The effects on human normal nasal epithelial cells (HNEpCs) following treatment with EPS T14 was evaluated at different time points and with increasing concentration of compound. To assess the antiviral properties, viability of HNEpCs treated with EPS T14 was analysed following infection with different respiratory viruses.</p><p><strong>Results: </strong>Neither toxicity nor pro-inflammatory properties were observed in vitro on HNEpCs treated with EPS T14 up to high concentrations, thus ensuring its safety. Cell culture-based assays revealed that treatment of HNEpCs with EPS T14 (used at 400ug/mL) results in efficient prevention of cell infection by different respiratory viruses through physically hindering the entry of the viruses via cell surface receptors. Interestingly, in addition to this prophylactic antiviral activity, EPS T14 also shows a long-lasting efficacy by inhibiting viral spread in the cell culture. Finally, combination of EPS T14 with a hypertonic saline solution shows a synergistic antiviral activity.</p><p><strong>Conclusion: </strong>EPS T14 can exert both prophylactic and therapeutic antiviral activity by blocking viral attachment to cellular receptors and could therefore represent a promising antiviral agent for preventing infections by different respiratory viruses.</p>","PeriodicalId":30986,"journal":{"name":"ImmunoTargets and Therapy","volume":null,"pages":null},"PeriodicalIF":6.2,"publicationDate":"2024-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11446858/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142373104","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}
引用次数: 0
Thrombopoietin Receptor Agonists in Post-Hematopoietic Cell Transplantation Complicated by Prolonged Thrombocytopenia: A Comprehensive Review. 血小板生成素受体激动剂在造血细胞移植后并发长期血小板减少症中的应用:全面回顾。
IF 6.2
ImmunoTargets and Therapy Pub Date : 2024-09-13 eCollection Date: 2024-01-01 DOI: 10.2147/ITT.S463384
Abdelrahman Elsayed, Basant Elsayed, Mohamed Elmarasi, Ahmed Adel Elsabagh, Engy Elsayed, Ibrahim Elmakaty, Mohamed Yassin
{"title":"Thrombopoietin Receptor Agonists in Post-Hematopoietic Cell Transplantation Complicated by Prolonged Thrombocytopenia: A Comprehensive Review.","authors":"Abdelrahman Elsayed, Basant Elsayed, Mohamed Elmarasi, Ahmed Adel Elsabagh, Engy Elsayed, Ibrahim Elmakaty, Mohamed Yassin","doi":"10.2147/ITT.S463384","DOIUrl":"https://doi.org/10.2147/ITT.S463384","url":null,"abstract":"<p><p>Hematopoietic cell transplantation (HCT) is a well-established procedure that has become a therapeutic mainstay for various hematological conditions. Prolonged thrombocytopenia following HCT is associated with a significant risk of morbidity and mortality, yet no universally recognized treatment protocol exists for such a complication. First-generation thrombopoietin receptor (TpoR) agonists as well as second-generation agents are known for their role in enhancing platelet production, and their use is expanding across various thrombocytopenic conditions. Therefore, we conducted this comprehensive review of the literature to provide an updated evaluation of the use of TpoR agonists and explore their efficacy and safety in the treatment of extended post-HCT thrombocytopenia. The literature search was conducted using PubMed database from 1996 through December 2023, using a predefined strategy with medical subject headings terms. We identified 64 reports on the utility of TpoR agonists, five of them were randomized controlled trials and the rest were retrospective observational studies and case series, with a total number of 1730 patients. Second-generation TpoR agonists appear more convenient than subcutaneous recombinant human thrombopoietin (rhTpo) as they can be orally administered and exhibit similar efficacy in platelet recovery, as indicated by recent trial results. Among these agents, avatrombopag, unlike eltrombopag, does not require any dietary restrictions, which could be more favorable for patients. However, eltrombopag remains the most extensively studied agent. TpoR agonists had promising effects in the treatment of post-HCT thrombocytopenia with a good safety profile so far, highlighting the potential benefit of their use.</p>","PeriodicalId":30986,"journal":{"name":"ImmunoTargets and Therapy","volume":null,"pages":null},"PeriodicalIF":6.2,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11407319/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142297094","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}
引用次数: 0
0
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
相关产品
×
本文献相关产品
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信