Frontiers in Immunology最新文献

{"title":"Identification of early predictive biomarkers for severe cytokine release syndrome in pediatric patients with chimeric antigen receptor T-cell therapy","authors":"Meng Su, Luoquan Chen, Li Xie, Aurore Fleurie, Renaud Jonquieres, Qing Cao, Benshang Li, Ji Liang, Yanjing Tang","doi":"10.3389/fimmu.2024.1450173","DOIUrl":"https://doi.org/10.3389/fimmu.2024.1450173","url":null,"abstract":"CAR-T cell therapy is a revolutionary new treatment for hematological malignancies, but it can also result in significant adverse effects, with cytokine release syndrome (CRS) being the most common and potentially life-threatening. The identification of biomarkers to predict the severity of CRS is crucial to ensure the safety and efficacy of CAR-T therapy. To achieve this goal, we characterized the expression profiles of seven cytokines, four conventional biochemical markers, and five hematological markers prior to and following CAR-T cell infusion. Our results revealed that IL-2, IFN-γ, IL-6, and IL-10 are the key cytokines for predicting severe CRS (sCRS). Notably, IL-2 levels rise at an earlier stage of sCRS and have the potential to serve as the most effective cytokine for promptly detecting the condition’s onset. Furthermore, combining these cytokine biomarkers with hematological factors such as lymphocyte counts can further enhance their predictive performance. Finally, a predictive tree model including lymphocyte counts, IL-2, and IL-6 achieved an accuracy of 85.11% (95% CI = 0.763–0.916) for early prediction of sCRS. The model was validated in an independent cohort and achieved an accuracy of 74.47% (95% CI = 0.597–0.861). This new prediction model has the potential to become an effective tool for assessing the risk of CRS in clinical practice.","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":null,"pages":null},"PeriodicalIF":7.3,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142222507","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Monocytes as an early risk factor for acute graft-versus-host disease after allogeneic hematopoietic stem cell transplantation","authors":"Huimin Sun, Linjie Wu, Xueying Zhao, Yingying Huo, Peiyuan Dong, Aiming Pang, Yawei Zheng, Yiwen Han, Shihui Ma, Erlie Jiang, Fang Dong, Tao Cheng, Sha Hao","doi":"10.3389/fimmu.2024.1433091","DOIUrl":"https://doi.org/10.3389/fimmu.2024.1433091","url":null,"abstract":"Acute graft-versus-host disease (aGVHD) is a major complication after allogeneic hematopoietic stem cell transplantation (allo-HSCT) and contributes to high morbidity and mortality. However, our current understanding of the development and progression of aGVHD after allo-HSCT remains limited. To identify the potential biomarkers for the prevention and treatment of aGVHD during the early hematopoietic reconstruction after transplantation, we meticulously performed a comparative analysis of single-cell RNA sequencing data from post-transplant patients with or without aGVHD. Prior to the onset of aGVHD, monocytes in the peripheral blood of patients with aGVHD experienced a dramatic rise and activation on day 21 post-transplantation. This phenomenon is closely aligned with clinical cohort results obtained from blood routine examinations. Furthermore, <jats:italic>in vitro</jats:italic> co-culture experiments showed that peripheral blood monocytes extracted from patients with aGVHD approximately 21 days post-transplantation induced a significantly higher proliferation rate of allogeneic T cells compared to those from patients without aGVHD. Our study indicates that monocytes could be a crucial early clinical risk factor for the development of aGVHD, and this insight could potentially guide the timing of monitoring efforts, recommending assessments at the pivotal juncture of approximately day 21 post-transplantation, shedding fresh light on the significance of early hematopoietic regeneration in relation to the onset of aGVHD.","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":null,"pages":null},"PeriodicalIF":7.3,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142222505","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Whole transcriptome landscape in HAPE under the stress of environment at high altitudes: new insights into the mechanisms of hypobaric hypoxia tolerance","authors":"Qiong Li, Fujin Fang, Chuanli Yang, Dong Yu, Qianhui Gong, Xiaobing Shen","doi":"10.3389/fimmu.2024.1444666","DOIUrl":"https://doi.org/10.3389/fimmu.2024.1444666","url":null,"abstract":"BackgroundHigh altitude pulmonary edema (HAPE) is an idiopathic, noncardiogenic form of pulmonary edema that occurs at high altitudes. It is characterized by a severe clinical course and carries a significant mortality risk. Despite its clinical relevance, the molecular mechanisms underlying HAPE are not well understood.MethodsWe conducted whole-transcriptome RNA sequencing on blood samples from 6 pairs of HAPE patients and healthy controls to identify differentially expressed (DE) mRNAs, miRNAs, circRNAs, lncRNAs, along with alternative splicing (AS) events, gene fusions, and novel transcripts. To explore the regulatory dynamics, we constructed ceRNA networks and analyzed immune cell infiltration patterns, further annotating the biological functions of these transcripts. For empirical validation, we selected five circRNAs from the ceRNA network and conducted RT-qPCR on 50 paired samples. Additionally, we assessed the correlations between circRNA expression levels and clinical data to evaluate their diagnostic potential.ResultsWe observed 2,023 differentially expressed mRNAs (DEmRNAs), 84 DEmiRNAs, 200 DEcircRNAs, and 3,573 DElncRNAs. A total of 139 ‘A3SS’ events, 103 ‘A5SS’ events, 545 ‘MXE’ events, 14 ‘RI’ events, and 1,482 ‘SE’ events were identified in the AS events analysis between the two groups. Two ceRNA networks were constructed. T cells, follicular helper, and Macrophages M1 cells exhibited the strongest positive correlation (R=0.82), while naive B cells and memory B cells demonstrated the strongest negative correlation (R=-0.62). In total, the expression of three circRNAs was significantly different in a larger cohort. Hsa_circ_0058497, hsa_circ_0081006, and hsa_circ_0083220 demonstrated consistent with the RNA sequencing results. These three circRNAs strongly correlate with clinical indicators and exhibit potential as diagnostic biomarkers. Finally, we verified five genes (CXCR4, HSD17B2, ANGPTL4, TIMP3, N4BP3) that were differentially expressed in endothelial cells under normoxia and hypoxia through bioinformatics and RT-qPCR analyses.ConclusionThis study elucidates the differential expression of coding and non-coding RNAs (ncRNAs) in HAPE, identifies new transcripts and genes, and enhances our understanding of the transcriptional characteristics of HAPE. Moreover, it highlights the potential role of circRNAs in advancing the diagnosis and treatment of HAPE.","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":null,"pages":null},"PeriodicalIF":7.3,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142222489","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CXCR1 and CXCR2 are potential neutrophil extracellular trap-related treatment targets in ulcerative colitis: insights from Mendelian randomization, colocalization and transcriptomic analysis","authors":"Yichuan Xv, Yiyi Feng, Jiang Lin","doi":"10.3389/fimmu.2024.1425363","DOIUrl":"https://doi.org/10.3389/fimmu.2024.1425363","url":null,"abstract":"ObjectivesThere is already substantial evidence indicating that neutrophil extracellular trap (NET) formation contributes to the inflammatory cascade in ulcerative colitis (UC). However, the precise regulatory mechanisms governing this process remain elusive. This study aimed to determine the role of NET-related genes in UC and reveal possible mechanisms.MethodsEmploying a two-sample MR methodology, we investigated the correlations between NET-associated genes (NRGs) and UC with summary data derived from a genome-wide association study (12,366 cases vs. 33,609 controls) and FinnGen (8,279 cases vs. 261,098 controls). The main analysis employed the inverse variance weighted method, supplemented by the MR-Egger method and weighted median method. Sensitivity analysis was conducted to rule out the interference of heterogeneity and pleiotropy among utilized instrument variables. The colocalization analysis was used to determine whether the identified NRGs and UC shared casual variants. Cross-tissue expression analysis was performed to characterize the expression patterns of target NRGs, while multi-gene correlation analysis and GSEA analysis were conducted to explore the mechanisms by which target NRGs promote UC and NET formation. Immunohistochemistry was used to validate the protein expression of target NRGs in the colon tissue of UC patients.ResultsAfter the validation of two datasets, seven NRGs were associated with the risk of UC. The higher expression of ITGB2 was associated with increased UC risk, while the expression of CXCR1, CXCR2, IRAK4, MAPK3, SIGLEC14, and SLC22A4 were inversely associated with UC risk. Colocalization analysis supported the correlation between CXCR1/2 and UC risk. Expression analysis indicated that CXCR1/2 were down-regulated in peripheral blood, but up-regulated in colon tissue. GSEA analysis and correlation analysis indicated that CXCR1/2 promoted UC and NET formation through neutrophil chemotaxis and PAD4-mediated pathways, separately. Immunohistochemical results confirmed the high expression of CXCR1/2 in colon tissues of UC patients.ConclusionsOur study identified CXCR1/2 as candidate targets in UC among all NRGs through multi-method argumentation, providing new insights of the regulation mechanisms of NET formation in the pathogenesis of UC.","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":null,"pages":null},"PeriodicalIF":7.3,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142222491","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Peripheral NK cell phenotypic alteration and dysfunctional state post hepatitis B subviral particles stimulation in CHB patients: evading immune surveillance","authors":"Mohamed A Selim, Reda A. Suef, Ebrahim Saied, Mostafa A. Abdel-Maksoud, Saeedah Musaed Almutairi, Mohammed Aufy, Adel A. Mousa, Mohamed T. M. Mansour, Mohamed M. S. Farag","doi":"10.3389/fimmu.2024.1427519","DOIUrl":"https://doi.org/10.3389/fimmu.2024.1427519","url":null,"abstract":"BackgroundThe relationship between chronic hepatitis B (CHB) infection and natural killer (NK) cell dysfunction is well-established, but the specific role of HBV viral antigens in driving NK cell impairment in patients with CHB remains unclear. This study investigates the modulatory effects of hepatitis B virus subviral particles (HBVsvp, a representative model for HBsAg) on the phenotypic regulation (activating and inhibitory receptors), cytokine production and cytotoxic potential of peripheral blood mononuclear cell-derived natural killer cells (PBMCs-derived NK cell), which contributes to NK cell dysfunction in CHB infection, potentially serving as an effective HBV immune evasion strategy by the virus.MethodsNK cells were isolated from peripheral blood of patients with CHB (n=5) and healthy individuals (n=5), stimulated with HBVsvp. Subsequent flow cytometric characterization involved assessing changes in activating (NKp46 and NKG2D) and inhibitory (CD94) receptors expression, quantifying TNF-α and IFN- γ cytokine secretion, and evaluating the cytotoxic response against HepG2.2.15 cells with subsequent HBVsvp quantification.ResultsIn CHB patients, <jats:italic>in vitro</jats:italic> exposure of PBMCs-derived NK cell with HBVsvp (represent HBsAg model) significantly reduced NK cell-activating receptors expression (P = 0.022), increased expression of CD94 <jats:sup>+</jats:sup> NK cells (p = 0.029), accompanied with a reduced TNF-α - IFN-γ cytokine levels, and impaired cytotoxic capacity (evidenced by increased cell proliferation and elevated HBVsvp levels in co-cultures with HepG2.2.15 cells in a time-dependent), relative to healthy donors.ConclusionThese findings suggest that HBVsvp may induce dysfunctional NK cell responses characterized by phenotypic imbalance with subsequent reduction in cytokine and cytotoxic levels, indicating HBVsvp immunosuppressive effect that compromises antiviral defense in CHB patients. These data enhance our understanding of NK cell interactions with HBsAg and highlight the potential for targeting CD94 inhibitory receptors to restore NK cell function as an immunotherapeutic approach. Further clinical research is needed to validate these observations and establish their utility as reliable biomarkers.","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":null,"pages":null},"PeriodicalIF":7.3,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142222490","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification of cellular senescence-related genes and immune cell infiltration characteristics in intervertebral disc degeneration","authors":"Muyi Wang, Hao Wang, Xin Wang, Yifei Shen, Dong Zhou, Yuqing Jiang","doi":"10.3389/fimmu.2024.1439976","DOIUrl":"https://doi.org/10.3389/fimmu.2024.1439976","url":null,"abstract":"BackgroundIntervertebral disc degeneration (IDD) progression involves multiple factors, including loss of nucleus pulposus cells and extracellular matrix as the basic pathological mechanism of degeneration, and is closely related to cellular senescence and immune cell infiltration. The aim of study was to identify critical cellular senescence-related genes and immune cell infiltration characteristics in IDD.MethodsFour datasets, including GSE70362, GSE112216, GSE114169, and GSE150408, were downloaded from the Gene Expression Omnibus database. The senescence-related genes were acquired from the CellAge Database and intersected with differentially expressed genes (DEGs) between IDD and control samples for senescence-related DEGs (SRDEGs). Protein-protein interaction (PPI) network analysis was performed to obtain ten hub SRDEGs. A consensus cluster analysis based on these hub genes was performed to divide the patients into clusters. The functional enrichment, and immune infiltration statuses of the clusters were compared. Weighted gene co-expression network analysis was used to identified key gene modules. The overlapping genes from key modules, DEGs of clusters and hub SRDEGs were intersected to obtain potential biomarkers. To verify the expression of potential biomarkers, quantitative polymerase chain reaction (qPCR) and immunohistochemistry were performed by using human intervertebral disc tissues.ResultsIn the GSE70362 dataset, a total of 364 DEGs were identified, of which 150 were upregulated and 214 were downregulated, and 35 genes were selected as SRDEGs. PPI analysis revealed ten hub SRDEGs and consensus cluster analysis divided the patients into two clusters. Compared to Cluster 2, Cluster 1 was highly enriched in extracellular matrix organization and various metabolic process. The level of Follicular T helper cells in the Cluster 1 was significantly higher than that in the Cluster 2. IGFBP3 and NQO1 were identified as potential biomarkers. The remaining 3 datasets, and the result of qPCR and immunohistochemistry showed that the expression levels of NQO1 and IGFBP3 in the degenerated group were higher than those in the control or treatment groups.ConclusionSenescence-related genes play a key role in the development and occurrence of IDD. IGFBP3 and NQO1 are strongly correlated with immune infiltration in the IDD and could become novel therapeutic targets that prevent the progression of IDD.","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":null,"pages":null},"PeriodicalIF":7.3,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142222531","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Fifty years of HLA-associated type 1 diabetes risk: history, current knowledge, and future directions","authors":"Janelle A. Noble","doi":"10.3389/fimmu.2024.1457213","DOIUrl":"https://doi.org/10.3389/fimmu.2024.1457213","url":null,"abstract":"More than 50 years have elapsed since the association of human leukocyte antigens (HLA) with type 1 diabetes (T1D) was first reported. Since then, methods for identification of HLA have progressed from cell based to DNA based, and the number of recognized HLA variants has grown from a few to tens of thousands. Current genotyping methodology allows for exact identification of all HLA-encoding genes in an individual’s genome, with statistical analysis methods evolving to digest the enormous amount of data that can be produced at an astonishing rate. The HLA region of the genome has been repeatedly shown to be the most important genetic risk factor for T1D, and the original reported associations have been replicated, refined, and expanded. Even with the remarkable progress through 50 years and over 5,000 reports, a comprehensive understanding of all effects of HLA on T1D remains elusive. This report represents a summary of the field as it evolved and as it stands now, enumerating many past and present challenges, and suggests possible paradigm shifts for moving forward with future studies in hopes of finally understanding all the ways in which HLA influences the pathophysiology of T1D.","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":null,"pages":null},"PeriodicalIF":7.3,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142222508","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pregnancy-related factors induce immune tolerance through regulation of sCD83 release","authors":"Pauline Krupa, Hannah Wein, Lea Sophie Zemmrich, Marek Zygmunt, Damián Oscar Muzzio","doi":"10.3389/fimmu.2024.1452879","DOIUrl":"https://doi.org/10.3389/fimmu.2024.1452879","url":null,"abstract":"A well-balanced maternal immune system is crucial to maintain fetal tolerance in case of infections during pregnancy. Immune adaptations include an increased secretion of soluble mediators to protect the semi-allogeneic fetus from excessive pro-inflammatory response. B lymphocytes acquire a higher capacity to express CD83 and secrete soluble CD83 (sCD83) upon exposure to bacteria-derived components such as LPS. CD83 possesses immune modulatory functions and shows a promising therapeutic potential against inflammatory conditions. The administration of sCD83 to pregnant mice reduces LPS-induced abortion rates. The increased CD83 expression by endometrial B cells as compared to peripheral blood B cells suggests its modulatory role in the fetal tolerance, especially in the context of infection. We postulate that in pregnancy, CD83 expression and release is controlled by pregnancy-related hormones. The intra- and extracellular expression of CD83 in leukocytes from peripheral blood or <jats:italic>decidua basalis</jats:italic> and <jats:italic>parietalis</jats:italic> at term were analyzed by flow cytometry. After treatment with pregnancy-related hormones and LPS, ELISA and qPCR were performed to study sCD83 release and <jats:italic>CD83</jats:italic> gene expression, respectively. Cleavage prediction analysis was used to find potential proteases targeting CD83. Expression of selected proteases was analyzed by ELISA. Higher levels of CD83 were found in CD11c<jats:sup>+</jats:sup> dendritic cells, CD3<jats:sup>+</jats:sup> T cells and CD19<jats:sup>+</jats:sup> B cells from <jats:italic>decidua basalis</jats:italic> and <jats:italic>decidua parietalis</jats:italic> after LPS-stimulation <jats:italic>in vitro</jats:italic>. An increase of intracellular expression of CD83 was also detected in CD19<jats:sup>+</jats:sup> B cells from both compartments. Stimulated B cells displayed significantly higher percentages of CD83<jats:sup>+</jats:sup> cells than dendritic cells and T cells from <jats:italic>decidua basalis</jats:italic> and peripheral blood. Treatment of B lymphocytes with pregnancy-related molecules (E2, P4, TGF-β1 and hCG) enhanced the LPS-mediated increase of CD83 expression, while dexamethasone led to a reduction. Similarly, the release of sCD83 was increased under TGF-β1 treatment but decreased upon dexamethasone stimulation. Finally, we found that the hormonal regulation of CD83 expression is likely a result from a balance between gene transcription from <jats:italic>CD83</jats:italic> and the modulation of the metalloproteinase MMP-7. Thus, data supports and complements our previous murine studies on hormonal regulation of CD83 expression, reinforcing its immunomodulatory relevance in anti-bacterial responses during pregnancy.","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":null,"pages":null},"PeriodicalIF":7.3,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142222488","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of aging on the frequency, phenotype, and function of CD4+ T cells in the human female reproductive tract","authors":"Zheng Shen, Landon G. vom Steeg, Mickey V. Patel, Marta Rodriguez-Garcia, Charles R. Wira","doi":"10.3389/fimmu.2024.1465124","DOIUrl":"https://doi.org/10.3389/fimmu.2024.1465124","url":null,"abstract":"Since CD4+ T cells are essential for regulating adaptive immune responses and for long lasting mucosal protection, changes in CD4+ T cell numbers and function are likely to affect protective immunity. What remains unclear is whether CD4+ T cell composition and function in the female reproductive tract (FRT) changes as women age. Here we investigated the changes in the composition and function of CD4+ T cells in the endometrium (EM), endocervix (CX), and ectocervix (ECX) with aging. We observed a significant decrease in both the total number and percentage of CD4+ T cells in the EM with increasing age, particularly in the years following menopause. CD4+ T cells within the FRT predominantly expressed CD69. The proportion of CD69+CD4+ T cells increased significantly with increasing age in the EM, CX and ECX. The composition of T helper cell subsets within the EM CD4+ T cell population also showed age-related changes. Specifically, there was a significant increase in the proportion of Th1 cells and a significant decrease in Th17 and Treg cells with increasing age. Furthermore, the production of IFNγ by CD4+ T cells in the EM, CX, and ECX significantly decreased with increasing age upon activation. Our findings highlight the complex changes occurring in CD4+ T cell frequency, phenotype, and function within the FRT as women age. Understanding these age-related immune changes in the FRT is crucial for enhancing our knowledge of reproductive health and immune responses in women.","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":null,"pages":null},"PeriodicalIF":7.3,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142222473","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A CD8+ T cell related immune score predicts survival and refines the risk assessment in acute myeloid leukemia","authors":"Zeyi Li, Peng Jin, Rufang Xiang, Xiaoyang Li, Jie Shen, Mengke He, Xiaxin Liu, Hongming Zhu, Shishuang Wu, Fangyi Dong, Huijin Zhao, Han Liu, Zhen Jin, Junmin Li","doi":"10.3389/fimmu.2024.1408109","DOIUrl":"https://doi.org/10.3389/fimmu.2024.1408109","url":null,"abstract":"Although advancements in genomic and epigenetic research have deepened our understanding of acute myeloid leukemia (AML), only one-third of patients can achieve durable remission. Growing evidence suggests that the immune microenvironment in bone marrow influences prognosis and survival in AML. There is a specific association between CD8<jats:sup>+</jats:sup> T cells and the prognosis of AML patients. To develop a CD8<jats:sup>+</jats:sup> T cell-related immune risk score for AML, we first evaluated the accuracy of CIBERSORTx in predicting the abundance of CD8<jats:sup>+</jats:sup> T cells in bulk RNA-seq and found it significantly correlated with observed single-cell RNA sequencing data and the proportions of CD8<jats:sup>+</jats:sup> T cells derived from flow cytometry. Next, we constructed the CTCG15, a 15-gene prognostic signature, using univariate and LASSO regression on the differentially expressed genes between CD8<jats:sup>+</jats:sup> T<jats:sup>High</jats:sup> and CD8<jats:sup>+</jats:sup> T<jats:sup>Low</jats:sup> groups. The CTCG15 was further validated across six datasets in different platforms. The CTCG15 has been shown to be independent of established prognostic markers, and can distill transcriptomic consequences of several genetic abnormalities closely related to prognosis in AML patients. Finally, integrating this model into the 2022 European LeukemiaNet contributed to a higher predictive power for prognosis prediction. Collectively, our study demonstrates that CD8<jats:sup>+</jats:sup> T cell-related signature could improve the comprehensive risk stratification and prognosis prediction in AML.","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":null,"pages":null},"PeriodicalIF":7.3,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142222474","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}