ImmunoTargets and Therapy最新文献

{"title":"Integrated Analysis of Single-Cell and Bulk RNA-Sequencing Based on EcoTyper Machine Learning Framework Identifies Cell-State-Specific M2 Macrophage Markers Associated with Gastric Cancer Prognosis.","authors":"A-Kao Zhu, Guang-Yao Li, Fang-Ci Chen, Jia-Qi Shan, Yu-Qiang Shan, Chen-Xi Lv, Zhi-Qiang Zhu, Yi-Ren He, Lu-Lu Zhai","doi":"10.2147/ITT.S490075","DOIUrl":"10.2147/ITT.S490075","url":null,"abstract":"<p><strong>Background: </strong>Tumor is a complex and dynamic ecosystem formed by the interaction of numerous diverse cells types and the microenvironments they inhabit. Determining how cellular states change and develop distinct cellular communities in response to the tumor microenvironment is critical to understanding cancer progression. Tumour-associated macrophages (TAMs) are an important component of the tumour microenvironment and play a crucial role in cancer progression. This study was designed to identify cell-state-specific M2 macrophage markers associated with gastric cancer (GC) prognosis through integrative analysis of single-cell RNA sequencing (scRNA-seq) and bulk RNA-seq data using a machine learning framework named EcoTyper.</p><p><strong>Results: </strong>The results showed that TAMs were classified into M1 macrophages, M2 macrophages, monocytes, undefined macrophages and dendritic cells, with M2 macrophages predominating. EcoTyper assigned macrophages to different cell states and ecotypes. A total of 168 cell-state-specific M2 macrophage markers were obtained by integrative analysis of scRNA-seq and bulk RNA-seq data. These markers could categorize GC patients into two clusters (clusters A and B) with different survival and M2 macrophages infiltration abundance. Cell adhesion molecules, cytokine-cytokine receptor interaction, JAK/STAT pathway, MAPK pathway were significantly enriched in cluster A, which had worse survival and higher M2 macrophages infiltration.</p><p><strong>Conclusion: </strong>In conclusion, this study profiles a single-cell atlas of intratumor heterogeneity and defines the cell states and ecotypes of TAMs in GC. Furthermore, we have identified prognostically relevant cell-state-specific M2 macrophage markers. These findings provide novel insights into the tumor ecosystem and cancer progression.</p>","PeriodicalId":30986,"journal":{"name":"ImmunoTargets and Therapy","volume":"13 ","pages":"721-734"},"PeriodicalIF":6.2,"publicationDate":"2024-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11646439/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142830097","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":"Evolution of Hematobiochemical Profiles in Newly Diagnosed HIV Patients and HIV-TB Co-Infected Patients: Correlation with Immunological and Virological Status.","authors":"Nawaid Hussain Khan, Chaitenya Verma, Mirza Masroor Ali Beg, Shashi Nandar Kumar, Gaurav Kaushik, Hafiz Ahmad, Kudaibergen Osmonaliev, Vinay Kumar","doi":"10.2147/ITT.S495295","DOIUrl":"10.2147/ITT.S495295","url":null,"abstract":"<p><strong>Background: </strong>CD4+ cells, HIV-1 plasma viral load (PVL), and IFN-γ have been observed to enhance susceptibility in TB infection/reactivation among HIV-1 infected people, leading to unusual clinical manifestations. HIV-TB co-infection is significant for immunological and virological response, making it a great clinical challenge for patient management. The objective of this study was to explore the correlation among various hematological and biochemical profiles with CD4+ count and PVL in order to decipher mechanisms of TB development or reactivation in HIV-infected patients.</p><p><strong>Methods: </strong>In this cross-sectional study, we included 200 newly diagnosed treatment naïve HIV-1 infected patients, of which 118 were HIV-TB co-infected and 82 were HIV-alone. The CD4+ T count was determined using the BD FACS Count System, and the plasma HIV-1 viral load was estimated using the Abbott m2000 real-time platform. The hematobiochemical testing was performed on fully-automated analyzer ADVIA^® 560 and Cobas^® 501 Roche Diagnostics. Statistical software SPSS-2, Spearman correlation analysis was used for data analysis and a P-value less than 0.05 was considered statistically significant.</p><p><strong>Results: </strong>Declined hemoglobulin level positively correlated with CD4 counts (r = 0.229; p = 0.001), and a negative correlation was observed with HIV-1 plasma viral load (r = -0.171; p = 0.016). Moreover, the CD4+ count and HIV-1 plasma viral load (PVL) were also correlated to anomalies such as thrombocytopenia, leucopenia, eosinophils, neutrophils, ESR, potassium, Albumin, globulin, SGOT, uric acid. Studies also found significantly higher absolute neutrophil count, ESR, and serum fasting blood sugar, creatine, uric acid, total bilirubin, globulin, and alkaline phosphatase in HIV-TB co-infected patients.</p><p><strong>Conclusion and recommendation: </strong>The initial value of Hb, ESR, absolute neutrophil counts, serum calcium, uric acid, and potassium can be used as an early indicator for active tuberculosis (TB) and as a substitute marker for the course of HIV disease, especially in areas with low resources.</p>","PeriodicalId":30986,"journal":{"name":"ImmunoTargets and Therapy","volume":"13 ","pages":"691-705"},"PeriodicalIF":6.2,"publicationDate":"2024-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11645950/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142830096","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 Potential Value of RPS27A in Prognosis and Immunotherapy: From Pan-Cancer Analysis to Hepatocellular Carcinoma Validation.","authors":"Xingwang Kuai, Chenyu Wei, Xiaoqian He, Fengli Wang, Chunbin Wang, Juling Ji","doi":"10.2147/ITT.S493217","DOIUrl":"10.2147/ITT.S493217","url":null,"abstract":"<p><strong>Purpose: </strong>Elucidation of the potential value of ribosomal protein S27a (RPS27A) for prognosis and immunotherapy in pan-cancer analysis, and exploration of the oncogenic function of RPS27A on hepatocellular carcinoma (HCC) and macrophage polarization.</p><p><strong>Methods: </strong>A systematic analysis of the function and mechanism of RPS27A was conducted with R software and multiple public platforms, including UALCAN, HPA, TISIDB, TIMER, cBioPortal, cancerSEA, TIDE, and TIMSO databases. The RPS27A expression in human and mouse liver was detected by immunohistochemistry. The biological behavior of HCC cells was detected in vitro after RPS27A overexpression. The influence of RPS27A on macrophage polarization was detected by the coculturing assay.</p><p><strong>Results: </strong>RPS27A dysregulation was found in multiple cancer types, and RPS27A level was associated with clinicopathologic features and prognosis in human cancers. RPS27A affected cancer statuses and multiple signaling pathways, such as DNA repair, invasion, IL10 synthesis, and MAPK activation. RPS27A took part in regulations of genomic alterations and heterogeneity and was associated with tumor mutation burden, microsatellite instability, neoantigen and so on. RPS27A expression was connected to the immune subtypes, tumor purity and immune cell infiltration and participated in regulation of the immunotherapy response. RPS27A was upregulated in HCC tissues compared to normal liver tissues. RPS27A overexpression in HCC cells promoted the proliferation, migration, and invasion of cancer cells, and accelerated M2 polarization of macrophage.</p><p><strong>Conclusion: </strong>RPS27A had the potential to be a biomarker for diagnosis, prognosis and immunotherapy response in pan-cancer, and targeting RPS27A may provide new ideas for cancer immunotherapy.</p>","PeriodicalId":30986,"journal":{"name":"ImmunoTargets and Therapy","volume":"13 ","pages":"673-690"},"PeriodicalIF":6.2,"publicationDate":"2024-12-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11636265/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142819511","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":"Diminished Diversities and Clonally Expanded Sequences of T-Cell Receptors in Patients with Chronic Spontaneous Urticaria.","authors":"Xian He, Xueping Wen, Peng Ming He, Dan Liang, Lihong Yang, Yuping Ran, Zhixin Zhang","doi":"10.2147/ITT.S481361","DOIUrl":"10.2147/ITT.S481361","url":null,"abstract":"<p><strong>Objective: </strong>Studies establish a link between autoimmune factors and chronic spontaneous urticaria (CSU). T cells are crucial in immune-mediated diseases like CSU, and T-cell receptor (TCR) diversity could be pivotal in autoimmune responses. The clinical relevance of TCR variations in CSU is unknown, but understanding them may offer insights into CSU's pathogenesis and treatment.</p><p><strong>Methods: </strong>This cross-sectional study included 132 chronic urticaria (CU) patients versus 100 age-matched healthy donors (HD), with subgroup analyses on CU type, angioedema, allergic comorbidities, and anti-IgE therapy efficacy. Peripheral TCRβ repertoires were analyzed by high-throughput sequencing.</p><p><strong>Results: </strong>CSU patients showed reduced TCR diversity (lower D50) and increased large clone proportions than HD. Moreover, TCR diversity in CSU patients was significantly lower than in those with Chronic Inducible Urticaria (ClndU). There were also differences in variable (V) and joining (J) gene usage between CU and HD groups as well as CSU and ClndU groups. However, in subgroup analyses regarding angioedema, allergic comorbidities, and the efficacy of anti-IgE treatment, no significant differences were found in TCR diversity or large TCRβ clones. Notably, patients with treatment relapse or poor response to anti-IgE therapy had a higher proportion of positively charged CDR3. Additionally, age affected TCR diversity, but TIgE value, EOS counts, CU duration, and UAS7 score did not associate significantly with D50.</p><p><strong>Conclusion: </strong>CSU patients exhibit reduced TCR diversity and increased large clone proportions, indicating abnormal T cell activation. The TCR diversity differences and distinct V and J gene usage between CSU and ClndU may indicate different mechanisms in T lymphocyte-associated immune responses for these two subtypes of CU. The higher positive charge in CDR3 of relapsed or poorly responsive patients to anti-IGE treatment may indicate more antigen charge involvement. These findings provide new insights into the pathogenesis of CSU and potential future treatments.</p>","PeriodicalId":30986,"journal":{"name":"ImmunoTargets and Therapy","volume":"13 ","pages":"661-671"},"PeriodicalIF":6.2,"publicationDate":"2024-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11628316/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142808098","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":"Circ_0001944 Targets the miR-1292-5p/FBLN2 Axis to Facilitate Sorafenib Resistance in Hepatocellular Carcinoma by Impeding Ferroptosis.","authors":"FanJing Jing, YunYan Shi, Dong Jiang, Xiao Li, JiaLin Sun, Qie Guo","doi":"10.2147/ITT.S463556","DOIUrl":"https://doi.org/10.2147/ITT.S463556","url":null,"abstract":"<p><strong>Background: </strong>Sorafenib, an orally active potent tyrosine kinase inhibitor (TKI), represented a primary treatment in patients with advanced hepatocellular carcinoma (HCC). Unfortunately, sorafenib resistance was regarded as a huge obstacle for HCC treatment.</p><p><strong>Methods: </strong>RNA-sequencing including circRNA Sequencing (circRNA-Seq) for circular RNAs (circRNAs), miRNA Sequencing (miRNA-Seq) for microRNAs (miRNAs), as well as mRNA Sequencing (mRNA-Seq) for mRNAs in <i>sorafenib-resistant HCC cells vs sorafenib-sensitive HCC cells</i>, were performed. Then, interaction correlation analysis between differentially expressed circRNAs and miRNAs and their target genes in Huh7/SOR and SMMC7721/SOR cells was exhibited. The \"circRNA-miRNA-mRNA\" network was constructed through <i>the Cytoscape software application, Circular RNA Interactome</i> and <i>Targetscan prediction, RNA binding protein immunoprecipitation (RIP), RNA pull-down, and Dual luciferase reporter assay</i>. Furthermore, <i>mRNA-Seq, Gene Ontology (GO) function and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis</i> for the downstream genes involved in the \"circRNA-miRNA-mRNA\" network was implemented. <i>Iron detection assay, Lipid peroxidation quantification assay, ROS measurement assay, CCK-8 assay,</i> and <i>tumor challenge</i> in vivo were used to determine the mechanisms promoting sorafenib resistance in HCC, where the \"circRNA-miRNA-mRNA\" network is clearly involved in.</p><p><strong>Results: </strong>circ_0001944 and circ_0078607 with upregulation and 2 downregulated expressed circRNAs (circ_0002874 and circ_0069981), as well as 11 upregulated miRNAs including miR-193a-5p, miR-197-3p, miR-27a-5p, miR-551b-5p, miR-335-3p, miR-767-3p, miR-767-5p, miR-92a-1-5p, miR-92a-3p, miR-3940-3p, and miR-664b-3p and 3 downregulated expressed miRNAs (miR-1292-5p, let-7c-5p, and miR-99a-5p) in sorafenib-resistant HCC cells were determined. Among these non-coding RNAs (ncRNAs), circ_0001944 and miR-1292-5p should not be drop out of sight; circ_0001944 has been proved to target miR-1292-5p to inhibit its expression in HCC. Subsequent findings also raise that miR-1292-5p directly targeted the 3'-noncoding region (3'-UTR) of <i>Fibulin 2 (FBLN2)</i> mRNA. Furthermore, circ_0001944 targets the miR-1292-5p/FBLN2 axis to inhibit cell ferroptosis in which the indicated regulators associated with iron overload and lipid peroxidation were \"rearranged\". Most importantly, circ_0001944 advanced sorafenib resistance in HCC through mitigating ferroptosis, where the miR-1292-5p/FBLN2 axis cannot be left unrecognized.</p><p><strong>Conclusion: </strong>Circ_0001944 is a putative target for reversing sorafenib resistance in HCC. Our findings are expected to provide new targets and new directions for sorafenib sensitization in the treatment of HCC.</p>","PeriodicalId":30986,"journal":{"name":"ImmunoTargets and Therapy","volume":"13 ","pages":"643-659"},"PeriodicalIF":6.2,"publicationDate":"2024-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11611519/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142772964","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":"Novel Insights into Causal Effects of Lipid and Lipid-Lowering Targets with Autoimmune Thyroid Disease: A Mendelian Randomization Study.","authors":"Chang Su, Juan Tian, Xueqing He, Xiaona Chang, Guang Wang, Jia Liu","doi":"10.2147/ITT.S487319","DOIUrl":"10.2147/ITT.S487319","url":null,"abstract":"<p><strong>Background: </strong>Dyslipidemia has been implicated in the pathogenesis of several diseases, including thyroid dysfunction and immune disorders. However, whether circulating lipids and long-term use of lipid-lowering drugs influence the development of autoimmune thyroid disease (AITD) remains unclear. This study aims to evaluate the effects of lipid-lowering drugs on AITD and explore their potential mechanisms.</p><p><strong>Methods: </strong>Two-sample and two-step Mendelian randomization (MR) studies were performed to assess the causal relationships between circulating lipids (LDL-C, TC, TG, and ApoB) and seven lipid-lowering drug targets (<i>ApoB, CETP, HMGCR, LDLR, NPC1L1, PCSK9</i>, and <i>PPARα</i>) with AITD. Mediation analyses were conducted to explore potential mediating factors.</p><p><strong>Results: </strong>There was no clear causality between circulating lipids (ApoB, LDL-C, TC, and TG) and AITD (<i>p</i> > 0.05). <i>ApoB</i> inhibition is related to a reduced risk of autoimmune thyroiditis (AT) (OR = 0.462, <i>p</i>= 0.046), while <i>PCSK9</i> inhibition is related to reduced Graves' disease (GD) risk (OR = 0. 551, <i>p</i> = 0.033). Moreover, <i>PCSK9</i> inhibition (OR = 0.735, <i>p</i> = 0.003), <i>LDLR</i> inhibition (OR = 0.779, <i>p</i> = 0.027), and <i>NPC1L1</i> inhibition (OR = 0.599, <i>p</i> = 0.016) reduced the risk of autoimmune hypothyroidism (AIH). Mediation analysis showed that <i>NPC1L1</i> inhibition and <i>PCSK9</i> inhibition exerted effects on AIH through IL-4 and FGF-19 levels. And the effect of <i>PCSK9</i> inhibition on GD through TNF-β levels.</p><p><strong>Conclusion: </strong>There was no clear causality between circulating lipids (ApoB, LDL-C, TC, and TG) and AITD. Lipid-lowering drug target gene inhibitors reduced the AITD risk by modulating inflammatory factors.</p>","PeriodicalId":30986,"journal":{"name":"ImmunoTargets and Therapy","volume":"13 ","pages":"631-641"},"PeriodicalIF":6.2,"publicationDate":"2024-11-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11600951/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142739659","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 CRTH2 as a New PPARγ-Target Gene in T Cells Suggested CRTH2 Dependent Conversion of T_h2 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⁺ T lymphocytes and the CD4⁺ and CD8⁺ subpopulations was observed. Also, the numbers of anti-inflammatory, resolutive T_h2 cells and FoxP3-positive regulatory T cells (T_reg) were decreased. We observed an augmented PPARγ expression in CD4⁺ 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_h2 marker is a receptor for prostaglandin D and its metabolic degradation product 15-deoxy-∆12,14-prostaglandin J₂ (15d-PGJ₂), an established endogenous PPARγ agonist. In line, we observed an increased PPARγ transactivation in response to 15d-PGJ₂ treatment in HEK293T cells overexpressing CRTH2. Translating these data to primary T cells, we found that T_h2 differentiation was associated with an increased expression of CRTH2. Interestingly, these CRTH2⁺ T cells were prone to apoptosis.</p><p><strong>Conclusion: </strong>These mechanistic data suggest an involvement of PPARγ in T_h2 differentiation and T cell depletion in COVID-19 patients.</p>","PeriodicalId":30986,"journal":{"name":"ImmunoTargets and Therapy","volume":"13 ","pages":"595-616"},"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}

{"title":"Causality Between 91 Circulating Inflammatory Proteins and Various Asthma Phenotypes: A Mendelian Randomization Study.","authors":"Shiyao Zhang, Xiuying Zhang, Chenghao Wei, Lai Zhang, Zhaoyang Li","doi":"10.2147/ITT.S486676","DOIUrl":"https://doi.org/10.2147/ITT.S486676","url":null,"abstract":"<p><strong>Objective: </strong>To investigate the causal relationship between 91 circulating inflammatory proteins and Various asthma phenotypes by means of Mendelian randomization.</p><p><strong>Methods: </strong>Genome-wide association Studies (GWAS) of 91 inflammatory proteins were pooled from the Olink Target platform with 14,824 participants. Various asthma phenotypes were derived from the FinnGen Biobank. Inverse variance weighting (IVW) was used as the main method for MR Analysis, supplemented by Mr-Egger, Weighted median, Simple mode, and Weighted mode. The MR-Egger intercept term test and Cochran's Q test were used to test the polymorphism and heterogeneity of IVs, and visual analysis was carried out to draw scatter plots, funnel plots, and leave-out-one plots. The FDR correction was performed due to the possibility of a type 1 error.</p><p><strong>Results: </strong>Genetically predicted IVW results revealed a total of 30 data sets suggesting a potential causal relationship between circulating inflammatory proteins and asthma phenotypes. Among them, 2 results were still strongly positive after FDR correction. The level of CST5 (OR=1.184; 95% CI: 1.075-1.305; P=0.0001; P-FDR=0.028) is associated with an increased risk of non-allergic asthma. LIF-R (OR=0.723; 95% CI: 0.620-0.842; P=0.000; P-FDR=0.003) is associated with a reduced risk of asthma in children. There was no pleiotropy or heterogeneity in the remaining 16 results that suggested a potential causal relationship.</p><p><strong>Conclusion: </strong>Increased CST5 levels are associated with an increased risk of non-allergic asthma. LIF-R is associated with a reduced risk of asthma in children.</p>","PeriodicalId":30986,"journal":{"name":"ImmunoTargets and Therapy","volume":"13 ","pages":"617-629"},"PeriodicalIF":6.2,"publicationDate":"2024-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11546284/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142629521","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 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":"13 ","pages":"585-593"},"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}

{"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":"13 ","pages":"571-583"},"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}