BMC Immunology最新文献

{"title":"Antagonist anti-LIF antibody derived from naive human scFv phage library inhibited tumor growth in mice.","authors":"Shengyan Zhao, Han Deng, Ying Lu, Yiran Tao, David Li, Xiaohua Jiang, Xian Wei, Xiaofeng Chen, Fanxin Ma, Yuxi Wang, Lantu Gou, Jinliang Yang","doi":"10.1186/s12865-024-00636-w","DOIUrl":"10.1186/s12865-024-00636-w","url":null,"abstract":"<p><strong>Background: </strong>Leukemia inhibitory factor (LIF) is a multifunctional member of the IL-6 cytokine family that activates downstream signaling pathways by binding to the heterodimer consisting of LIFR and gp130 on the cell surface. Previous research has shown that LIF is highly expressed in various tumor tissues (e.g. pancreatic cancer, breast cancer, prostate cancer, and colorectal cancer) and promotes cancer cell proliferation, migration, invasion, and differentiation. Moreover, the overexpression of LIF correlates with poor clinicopathological characteristics. Therefore, we hypothesized that LIF could be a promising target for the treatment of cancer. In this work, we developed the antagonist antibody 1G11 against LIF and investigated its anti-tumor mechanism and its therapeutic efficacy in mouse models.</p><p><strong>Results: </strong>A series of single-chain variable fragments (scFvs) targeting LIF were screened from a naive human scFv phage library. These scFvs were reconstructed in complete IgG form and produced by the mammalian transient expression system. Among the antibodies, 1G11 exhibited the excellent binding activity to human, cynomolgus monkey and mouse LIF. Functional analysis demonstrated 1G11 could block LIF binding to LIFR and inhibit the intracellular STAT3 phosphorylation signal. Interestingly, 1G11 did not block LIF binding to gp130, another LIF receptor that is involved in forming the receptor complex together with LIFR. In vivo, intraperitoneal administration of 1G11 inhibited tumor growth in CT26 and MC38 models of colorectal cancer. IHC analysis demonstrated that p-STAT3 and Ki67 were decreased in tumor tissue, while c-caspase 3 was increased. Furthermore, 1G11 treatment improves CD3+, CD4 + and CD8 + T cell infiltration in tumor tissue.</p><p><strong>Conclusions: </strong>We developed antagonist antibodies targeting LIF/LIFR signaling pathway from a naive human scFv phage library. Antagonist anti-LIF antibody exerts antitumor effects by specifically reducing p-STAT3. Further studies revealed that anti-LIF antibody 1G11 increased immune cell infiltration in tumor tissues.</p>","PeriodicalId":9040,"journal":{"name":"BMC Immunology","volume":"25 1","pages":"56"},"PeriodicalIF":2.9,"publicationDate":"2024-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11340043/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142016323","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pre-treatment plasma retinol binding protein 4 level and its change after treatments predict systemic treatment response in psoriasis patients.","authors":"Runting Niu, Zhijia Li, Wanqing Jiang, Qingyan Yang, Xinfei Duan, Lixiao Sun, Zhijie Cheng, Junhui Huang, Lihong Li, Junge Ma, Taiping Hu, Lijuan Zhou, Juan Du, Chang Wang, Feifei Liu","doi":"10.1186/s12865-024-00647-7","DOIUrl":"10.1186/s12865-024-00647-7","url":null,"abstract":"<p><strong>Background: </strong>Retinol binding protein 4 (RBP4) is a mediator of inflammation and related to skin lesion formation, which suggests its engagement in psoriasis pathology and progression. This study intended to explore the change in RBP4 after systemic treatments, and its ability to predict treatment response in psoriasis patients.</p><p><strong>Methods: </strong>This prospective study enrolled 85 psoriasis patients and 20 healthy subjects. Plasma RBP4 was detected by enzyme-linked immunosorbent assay at baseline and 12th week (W12) after systemic treatments in psoriasis patients, as well as after enrollment in healthy subjects. Psoriasis Area and Severity Index (PASI) 75 and PASI 90 were evaluated at W12 in psoriasis patients.</p><p><strong>Results: </strong>RBP4 at baseline was higher in psoriasis patients than in healthy subjects [median (interquartile range): 13.39 (9.71-22.92) versus 9.59 (6.57-13.72) µg/mL] (P = 0.003). In psoriasis patients, 50 (58.8%) patients achieved PASI 75 at W12, and 25 (29.4%) patients achieved PASI 90 at W12. RBP4 was decreased at W12 compared to its level at baseline (P < 0.001). Lower RBP4 at baseline predicted achieving PASI 75 at W12 (P = 0.038). Greater RBP4 change (baseline-W12) precited achieving PASI 75 (P = 0.036) and PASI 90 (P = 0.045) at W12. Receiver operating characteristic curves suggested that after adjustment for all clinical features, RBP4 at baseline and RBP4 change (baseline-W12) had an acceptable ability to predict PASI 75 and PASI 90 at W12 with all area under curve values > 0.7.</p><p><strong>Conclusion: </strong>Plasma RBP4 is decreased after systemic treatments, and its low baseline level and greater decline after treatments predict good treatment response in psoriasis patients.</p>","PeriodicalId":9040,"journal":{"name":"BMC Immunology","volume":"25 1","pages":"55"},"PeriodicalIF":2.9,"publicationDate":"2024-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11337756/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142016324","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"KIR2DL1 gene is a surrogate marker of protection against infection-related hospitalization among HIV-1 unexposed versus exposed uninfected infants in Cameroon","authors":"Luc-Aimé Kagoué Simeni, Gabriel Loni Ekali, Clauvis Kunkeng Yengo, Rodrigue Kamga Wouambo, Janett Fischer, Oumarou M’rikam A. Bessong, Joseph Fokam, Louis-Marie Yindom, Jules Clément Assob Nguedia","doi":"10.1186/s12865-024-00645-9","DOIUrl":"https://doi.org/10.1186/s12865-024-00645-9","url":null,"abstract":"HIV-exposed uninfected infants (HEU) appear more vulnerable to infections compared to their HIV-unexposed uninfected (HUU) peers, generally attributed to poor passive immunity acquired from the mother. This may be due to some genetic factors that could alter the immune system. We thus sought to determine the distribution of Killer Cell Immunoglobulin-Like Receptors (KIRs) genes in HEU versus HUU and study their associations with the occurrence of infection-related hospitalization. A cohort study was conducted from May 2019 to April 2020 among HEU and HUU infants, including their follow-up at weeks 6, 12, 24, and 48, in reference pediatric centers in Yaoundé-Cameroon. The infant HIV status and infections were determined. A total of 15 KIR genes were investigated using the sequence-specific primer polymerase chain reaction (PCR-SSP) method. The KIR genes that were significantly associated with HIV-1 status (HEU and HUU) were analyzed for an association with infection-related hospitalizations. This was only possible if, and to the extent that, infection-related hospitalizations varied significantly according to status. Multivariate logistic regression analyses were conducted to determine the association between KIR gene content variants and HIV status, while considering a number of potential confounding factors. Furthermore, the risk was quantified using relative risk, odds ratio, and a 95% confidence interval. The Fisher exact test was employed to compare the frequency of occurrences. A p-value of less than 0.05 was considered statistically significant. In this cohort, a total of 66 infants participated, but only 19 acquired infections requiring hospitalizations (14.81%, 04/27 HUU and 38.46%, 15/39 HEU, p = 0.037). At week 48 (39 HEU and 27 HUU), the relative risk (RR) for infection-related hospitalizations was 2.42 (95% CI: 1.028–5.823) for HEU versus HUU with OR 3.59 (1.037–12.448). KIR2DL1 gene was significantly underrepresented in HEU versus HUU (OR = 0.183, 95%CI: 0.053–0.629; p = 0.003), and the absence of KIR2DL1 was significantly associated with infection-related hospitalization (p < 0.001; aOR = 0.063; 95%CI: 0.017–0.229). Compared to HUU, the vulnerability of HEU is driven by KIR2DL1, indicating the protective role of this KIR against infection and hospitalizations.","PeriodicalId":9040,"journal":{"name":"BMC Immunology","volume":"194 1","pages":""},"PeriodicalIF":3.0,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141863810","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Transcriptomics explores potential mechanisms for the development of Primary Sjogren's syndrome to diffuse large B-cell lymphoma in B cells.","authors":"Yanan Xu, Jianxing Han, Ziyi Fan, Shufen Liang","doi":"10.1186/s12865-024-00646-8","DOIUrl":"10.1186/s12865-024-00646-8","url":null,"abstract":"<p><strong>Purpose: </strong>Primary Sjogren's syndrome (pSS) is a prevalent autoimmune disease. The immune dysregulation it causes often leads to the development of diffuse large B-cell lymphoma (DLBCL) in clinical practice. However, how it contributes to these two disorders at the molecular level is not yet known. This study explored the potential molecular mechanisms associated with the differences between DLBCL and pSS.</p><p><strong>Patients and methods: </strong>Gene expression matrices from discovery cohort 1, discovery cohort 2, and the validation cohort were downloaded from the GEO and TCGA databases. Weighted gene coexpression network analysis (WGCNA) was performed to identify the coexpression modules of DLBCL and pSS in discovery cohort 1 and obtain shared genes. GO and KEGG enrichment analyses and PPI network analysis were performed on the shared genes. Immune-related genes (IRGs) were intersected with shared genes to obtain common genes. Afterward, common genes were identified via machine learning methods. The immune infiltration analysis, miRNA-TF-hub gene regulatory chart, gene interactions of the hub genes, and gene‒drug target analysis were performed. Finally, STAT1 was identified as a possible essential gene by the above analysis, and immune infiltration and GSEA pathway analyses were performed in the high- and low-expression groups in discovery cohort 2. The diagnostic efficacy of the hub genes was assessed in the validation cohort, and clinical samples were collected for validation.</p><p><strong>Results: </strong>By WGCNA, one modular gene in each group was considered highly associated with the disease, and we obtained 28 shared genes. Enrichment analysis revealed shared genes involved in the viral response and regulation. We obtained four hub genes (ISG20, STAT1, TLR7, and RSAD2) via the algorithm. Hub genes and similar genes are primarily involved in regulating type I IFNs. The construction of a miRNA-TF-hub gene regulatory chart revealed that hsa-mir-155-5p, hsa-mir-146b-5p, hsa-mir-21-3p, and hsa-mir-126-3p play essential roles in both diseases. Hub genes were differentially expressed in B-cell memory according to immune infiltration analysis. Hub genes had a strong diagnostic effect on both diseases. STAT1 plays an essential role in immune cells in both diseases.</p><p><strong>Conclusion: </strong>We identified hub susceptibility genes for DLBCL and pSS and identified hub genes and potential therapeutic targets that may act as biomarkers.</p>","PeriodicalId":9040,"journal":{"name":"BMC Immunology","volume":"25 1","pages":"53"},"PeriodicalIF":2.9,"publicationDate":"2024-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11287849/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141854712","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Serum immunoglobulin concentrations and risk of type 2 diabetes mellitus in adults: a prospective cohort study from the TCLSIH study.","authors":"Li Zhang, Yuanbin Li, Honglei Wang, Yirui Guo, Xiaotong Wang, Hongmei Wu, Qing Zhang, Li Liu, Ge Meng, Shunming Zhang, Shaomei Sun, Ming Zhou, Qiyu Jia, Kun Song, Anna Stubbendorff, Yeqing Gu, Kaijun Niu","doi":"10.1186/s12865-024-00637-9","DOIUrl":"10.1186/s12865-024-00637-9","url":null,"abstract":"<p><p>Type 2 diabetes mellitus (T2DM) is a metabolic disorder characterized by hyperglycemia resulting from defects in insulin secretion and/or insulin action. Increasing evidence suggests that inflammation played an important role in the pathogenesis of T2DM. Prospective studies on the link between immunoglobulins concentrations and the risk of T2DM in adults are limited. We developed a cohort study including 7,093 adults without T2DM history. The incidence of T2DM was 16.45 per 1,000 person-years. Compared with the lowest quartiles, the hazard ratios (95% confidence intervals) of T2DM for the highest quartiles of IgG, IgE, IgM and IgA were 0.64 (0.48-0.85), 0.94 (0.72-1.23), 0.68 (0.50-0.92) and 1.62 (1.24-2.11) (P for trend was < 0.01, 0.84, 0.02 and < 0.0001), respectively, suggesting that serum IgG and IgM concentrations were inversely associated with the incidence of T2DM, and IgA levels were positively associated with the risk of T2DM in a general adult population.</p>","PeriodicalId":9040,"journal":{"name":"BMC Immunology","volume":"25 1","pages":"52"},"PeriodicalIF":2.9,"publicationDate":"2024-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11285130/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141791839","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Histone acetylation risk model predicts prognosis and guides therapy selection in glioblastoma: implications for chemotherapy and anti-CTLA-4 immunotherapy","authors":"Xingyi Jin, Zhigang Qin, Hang Zhao","doi":"10.1186/s12865-024-00639-7","DOIUrl":"https://doi.org/10.1186/s12865-024-00639-7","url":null,"abstract":"Glioblastoma is characterized by high aggressiveness, frequent recurrence, and poor prognosis. Histone acetylation-associated genes have been implicated in its occurrence and development, yet their predictive ability in glioblastoma prognosis remains unclear. This study constructs a histone acetylation risk model using Cox and LASSO regression analyses to evaluate glioblastoma prognosis. We assessed the model’s prognostic ability with univariate and multivariate Cox regression analyses. Additionally, immune infiltration was evaluated using ESTIMATE and TIMER algorithms, and the SubMAP algorithm was utilized to predict responses to CTLA4 inhibitor. Multiple drug databases were applied to assess drug sensitivity in high- and low-risk groups. Our results indicate that the histone acetylation risk model is independent and reliable in predicting prognosis. Low-risk patients showed higher immune activity and longer overall survival, suggesting anti-CTLA4 immunotherapy suitability, while high-risk patients might benefit more from chemotherapy. This model could guide personalized therapy selection for glioblastoma patients.","PeriodicalId":9040,"journal":{"name":"BMC Immunology","volume":"24 1","pages":""},"PeriodicalIF":3.0,"publicationDate":"2024-07-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141770205","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multiplex array analysis of circulating cytokines and chemokines in COVID-19 patients during the first wave of the SARS-CoV-2 pandemic in Milan, Italy.","authors":"Estefanía Calvo-Alvarez, Sarah D'Alessandro, Nunzia Zanotta, Nicoletta Basilico, Silvia Parapini, Lucia Signorini, Federica Perego, Kevin Kamau Maina, Pasquale Ferrante, Annalisa Modenese, Pierluigi Pizzocri, Andrea Ronsivalle, Serena Delbue, Manola Comar","doi":"10.1186/s12865-024-00641-z","DOIUrl":"10.1186/s12865-024-00641-z","url":null,"abstract":"<p><strong>Background: </strong>The systemic inflammatory syndrome called \"cytokine storm\" has been described in COVID-19 pathogenesis, contributing to disease severity. The analysis of cytokine and chemokine levels in the blood of 21 SARS-CoV-2 positive patients throughout the phases of the pandemic has been studied to understand immune response dysregulation and identify potential disease biomarkers for new treatments. The present work reports the cytokine and chemokine levels in sera from a small cohort of individuals primarily infected with SARS-CoV-2 during the first wave of the COVID-19 pandemic in Milan (Italy).</p><p><strong>Results: </strong>Among the 27 cytokines and chemokines investigated, a significant higher expression of Interleukin-9 (IL-9), IP-10 (CXCL10), MCP-1 (CCL2) and RANTES (CCL-5) in infected patients compared to uninfected subjects was observed. When the change in cytokine/chemokine levels was monitored over time, from the hospitalization day to discharge, only IL-6 and IP-10 showed a significant decrease. Consistent with these findings, a significant negative correlation was observed between IP-10 and anti-Spike IgG antibodies in infected individuals. In contrast, IL-17 was positively correlated with the production of IgG against SARS-CoV-2.</p><p><strong>Conclusions: </strong>The cytokine storm and the modulation of cytokine levels by SARS-CoV-2 infection are hallmarks of COVID-19. The current global immunity profile largely stems from widespread vaccination campaigns and previous infection exposures. Consequently, the immunological features and dynamic cytokine profiles of non-vaccinated and primarily-infected subjects reported here provide novel insights into the inflammatory immune landscape in the context of SARS-CoV-2 infection, and offer valuable knowledge for addressing future viral infections and the development of novel treatments.</p>","PeriodicalId":9040,"journal":{"name":"BMC Immunology","volume":"25 1","pages":"49"},"PeriodicalIF":2.9,"publicationDate":"2024-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11282750/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141765397","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Immunological factors, important players in the development of asthma.","authors":"Yang Wang, Li Liu","doi":"10.1186/s12865-024-00644-w","DOIUrl":"10.1186/s12865-024-00644-w","url":null,"abstract":"<p><p>Asthma is a heterogeneous disease, and its development is the result of a combination of factors, including genetic factors, environmental factors, immune dysfunction and other factors. Its specific mechanism has not yet been fully investigated. With the improvement of disease models, research on the pathogenesis of asthma has made great progress. Immunological disorders play an important role in asthma. Previously, we thought that asthma was mainly caused by an imbalance between Th1 and Th2 immune responses, but this theory cannot fully explain the pathogenesis of asthma. Recent studies have shown that T-cell subsets such as Th1 cells, Th2 cells, Th17 cells, Tregs and their cytokines contribute to asthma through different mechanisms. For the purpose of the present study, asthma was classified into distinct phenotypes based on airway inflammatory cells, such as eosinophilic asthma, characterized by predominant eosinophil aggregates, and neutrophilic asthma, characterized by predominant neutrophil aggregates. This paper will examine the immune mechanisms underlying different types of asthma, and will utilize data from animal models and clinical studies targeting specific immune pathways to inform more precise treatments for this condition.</p>","PeriodicalId":9040,"journal":{"name":"BMC Immunology","volume":"25 1","pages":"50"},"PeriodicalIF":2.9,"publicationDate":"2024-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11282818/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141765396","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"TLR7 agonist, DSP-0509, with radiation combination therapy enhances anti-tumor activity and modulates T cell dependent immune activation.","authors":"Yosuke Ota, Ryosaku Inagaki, Yasuhiro Nagai, Yuko Hirose, Masashi Murata, Setsuko Yamamoto","doi":"10.1186/s12865-024-00643-x","DOIUrl":"10.1186/s12865-024-00643-x","url":null,"abstract":"<p><strong>Background: </strong>TLR7 is a key player in the antiviral immunity. TLR7 signaling activates antigen-presenting cells including DCs and macrophages. This activation results in the adaptive immunity including T cells and B cells. Therefore, TLR7 is an important molecule of the immune system. Based on these observations, TLR7 agonists considered to become a therapy weaponize the immune system against cancer. Radiation therapy (RT) is one of the standard cancer therapies and is reported to modulate the tumor immune response. In this study, we aimed to investigate the anti-tumor activity in combination of TLR7 agonist, DSP-0509, with RT and underlying mechanism.</p><p><strong>Result: </strong>We showed that anti-tumor activity is enhanced by combining RT with the TLR7 agonist DSP-0509 in the CT26, LM8, and 4T1 inoculated mice models. We found that once- weekly (q1w) dosing of DSP-0509 rather than biweekly (q2w) dosing is needed to achieve superior anti-tumor activities in CT26 model. Spleen cells from the mice in RT/DSP-0509 combination treatment group showed increased tumor lytic activity, inversely correlated with tumor volume, as measured by the chromium-release cytotoxicity assay. We also found the level of cytotoxic T lymphocytes (CTLs) increased in the spleens of completely cured mice. When the mice completely cured by combination therapy were re-challenged with CT26 cells, all mice rejected CT26 cells but accepted Renca cells. This rejection was not observed with CD8 depletion. Furthermore, levels of splenic effector memory CD8 T cells were increased in the combination therapy group. To explore the factors responsible for complete cure by combination therapy, we analyzed peripheral blood leukocytes (PBLs) mRNA from completely cured mice. We found that Havcr2^low, Cd274^low, Cd80^high, and Il6^low were a predictive signature for the complete response to combination therapy. An analysis of tumor-derived mRNA showed that combination of RT and DSP-0509 strongly increased the expression of anti-tumor effector molecules including Gzmb and Il12.</p><p><strong>Conclusion: </strong>These data suggest that TLR7 agonist, DSP-0509, can be a promising concomitant when used in combination with RT by upregulating CTLs activity and gene expression of effector molecules. This combination can be an expecting new radio-immunotherapeutic strategy in clinical trials.</p>","PeriodicalId":9040,"journal":{"name":"BMC Immunology","volume":"25 1","pages":"48"},"PeriodicalIF":2.9,"publicationDate":"2024-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11270965/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141757089","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The role of immune-inflammatory markers in children with complicated and uncomplicated malaria in Enugu, Nigeria.","authors":"Angela Ogechukwu Ugwu, Rebecca Chinyelu Chukwuanukwu, Friday Alfred Ehiaghe, Emmanuel Onyebuchi Ugwu","doi":"10.1186/s12865-024-00642-y","DOIUrl":"10.1186/s12865-024-00642-y","url":null,"abstract":"<p><strong>Background: </strong>There is currently insufficient data regarding immune parameters and relationship with severity of malaria infection in Enugu, Nigeria where the economic and social costs of the disease and its management are extremely high. This study was conducted to determine the relationship between malaria severity and some immune-inflammatory markers among malaria-infected children in Enugu, Nigeria.</p><p><strong>Methods: </strong>The study adopted a case control design. Eligible children were categorized into three groups - complicated, uncomplicated and healthy children. Pro-inflammatory cytokines -interferon-gamma (IFN-γ) and tumor necrosis factor-alpha (TNF-α); and anti-inflammatory cytokine - interleukin-10 (IL-10) were assayed using enzyme-linked immunosorbent assay (ELISA) technique, while immune cell ratios - neutrophil lymphocyte ratio (NLR) and monocyte lymphocyte ratio (MLR) were calculated from full blood count results.</p><p><strong>Results: </strong>The overall mean age of the participants was 7.3 ± 3.4 (range: 6 months - 12 years) and the male-female ratio was 1:1. There was no significant difference between the ages of the three groups (P = 0.44). The Mean levels of IFN-γ, TNF-α, and NLR were higher in complicated than uncomplicated malaria (266.9 ± 66.3pg/ml vs. 62.5 ± 6.4pg/ml, p < 0.001; 140.3 ± 30.0pg/ml vs. 42.0 ± 9.0pg/ml, p < 0.001; and 32.9 ± 16.2pg/ml vs. 17.8 ± 6.0pg/ml, p < 0.001, respectively); and higher in uncomplicated malaria than healthy children (62.5 ± 6.4pg/ml vs. 40.6 ± 9.1pg/ml, p < 0.001; 42.0 ± 9.0pg/ml vs. 105.7 ± 32.1, p < 0.001; 17.8 ± 6.0pg/ml vs. 18.7 ± 6.2pg/ml, p < 0.001, respectively). On the other hand, the mean level of IL-10 is higher in uncomplicated than complicated malaria (105.73 ± 32.06pg/ml vs. 40.60 ± 9.11pg/ml, p < 0.001). There was a positive correlation between NLR and IFN-γ (r = 0.815; p = 0.003), as well as NLR and TNF-α (r = 0.745; p = 0.002).</p><p><strong>Conclusion: </strong>Complicated malaria is associated with higher levels of pro-inflammatory cytokines while uncomplicated malaria is associated with higher levels of anti-inflammatory cytokines. NLR correlates positively with pro-inflammatory cytokines, and could be useful in evaluation for the severity of malaria infection.</p>","PeriodicalId":9040,"journal":{"name":"BMC Immunology","volume":"25 1","pages":"47"},"PeriodicalIF":2.9,"publicationDate":"2024-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11265479/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141747427","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}