Genes and immunity最新文献_第5页

The ability of microRNAs to regulate the immune response in ischemia/reperfusion inflammatory pathways microRNA 在缺血/再灌注炎症途径中调节免疫反应的能力。

IF 5 3区医学

Genes and immunity Pub Date : 2024-06-22 DOI: 10.1038/s41435-024-00283-6

Peter Artimovič, Ivana Špaková, Ema Macejková, Timea Pribulová, Miroslava Rabajdová, Mária Mareková, Martina Zavacká

引用次数: 0

Correction: Getting under the skin: resident memory CD8+ T cells have a second residence in the draining lymph node 更正：深入皮下：常驻记忆 CD8+ T 细胞在引流淋巴结有第二居所。

IF 5 3区医学

Genes and immunity Pub Date : 2024-06-19 DOI: 10.1038/s41435-024-00282-7

Teresa Neuwirth, Azuah L. Gonzalez, Emilie Fisher-Gupta, Georg Stary

引用次数: 0

PARP inhibitor and immune checkpoint inhibitor have synergism efficacy in gallbladder cancer PARP抑制剂和免疫检查点抑制剂对胆囊癌有协同疗效

IF 5 3区医学

Genes and immunity Pub Date : 2024-06-12 DOI: 10.1038/s41435-024-00280-9

Yu Chen, Xudong Fan, Ruohuang Lu, Shan Zeng, Pingping Gan

{"title":"PARP inhibitor and immune checkpoint inhibitor have synergism efficacy in gallbladder cancer","authors":"Yu Chen, Xudong Fan, Ruohuang Lu, Shan Zeng, Pingping Gan","doi":"10.1038/s41435-024-00280-9","DOIUrl":"10.1038/s41435-024-00280-9","url":null,"abstract":"Gallbladder cancer (GBC) is an aggressive cancer with poor prognosis. PARP inhibitors (PARPi) target PARP enzymes and have shown efficacy in patients with breast cancer gene (BRCA) mutations. Immunotherapy, especially immune checkpoint inhibitors (ICIs), has transformed cancer treatment. However, the combined impact of PARPi and ICIs in GBC remains unclear. We present a groundbreaking case of a GBC patient with BRCA2 mutations who received combination therapy with PARPi and ICIs after failing multiple lines of treatment. Next-generation sequencing (NGS-Seq) identified BRCA gene mutations. To further investigate potential mechanisms, we developed a PARP1-BRCA1-BRCA2 pathway-related risk score (PBscore) system to evaluate the impact of PARPi on the tumor immune microenvironment via RNA-Seq data. Gene expression and functional analysis identified potential mechanisms associated with the PBscore. Experimental validation assessed the impact of the combination therapy on the tumor microenvironment using multiplexed immunofluorescence imaging and immunohistochemistry in patients with BRCA gene wild type or mutations. RNA-Seq analysis revealed correlations between PBscore, immune checkpoint levels, tumor-infiltrating immune cells (TIICs), and the cancer-immunity cycle. Multiplexed immunofluorescence imaging validated that low PBscore patients might have an active tumor microenvironment. Furthermore, upon drug resistance, we observed an upregulation of negative immune checkpoints such as CEACAM1, indicating that the tumor immune microenvironment becomes suppressed after resistance. Our study revealed that PBscore could serve as a biomarker to predict immunotherapy efficacy, offering a promising alternative for BRCA2-mutated GBC patients.","PeriodicalId":12691,"journal":{"name":"Genes and immunity","volume":"25 4","pages":"307-316"},"PeriodicalIF":5.0,"publicationDate":"2024-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141310468","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Sphingomyelin-derived epacadostat nanovesicle enhances IDO1 inhibition for improved melanoma combination immunotherapy 鞘磷脂衍生的依帕卡托司他纳米囊泡可增强对 IDO1 的抑制，从而改善黑色素瘤联合免疫疗法。

IF 5 3区医学

Genes and immunity Pub Date : 2024-06-11 DOI: 10.1038/s41435-024-00281-8

Zhiren Wang, Wenpan Li, Jianqin Lu

引用次数: 0

Resolving haplotype variation and complex genetic architecture in the human immunoglobulin kappa chain locus in individuals of diverse ancestry 解析人类免疫球蛋白 kappa 链基因座中不同血统个体的单倍型变异和复杂遗传结构。

IF 5 3区医学

Genes and immunity Pub Date : 2024-06-06 DOI: 10.1038/s41435-024-00279-2

Eric Engelbrecht, Oscar L. Rodriguez, Kaitlyn Shields, Steven Schultze, David Tieri, Uddalok Jana, Gur Yaari, William D. Lees, Melissa L. Smith, Corey T. Watson

{"title":"Resolving haplotype variation and complex genetic architecture in the human immunoglobulin kappa chain locus in individuals of diverse ancestry","authors":"Eric Engelbrecht, Oscar L. Rodriguez, Kaitlyn Shields, Steven Schultze, David Tieri, Uddalok Jana, Gur Yaari, William D. Lees, Melissa L. Smith, Corey T. Watson","doi":"10.1038/s41435-024-00279-2","DOIUrl":"10.1038/s41435-024-00279-2","url":null,"abstract":"Immunoglobulins (IGs), critical components of the human immune system, are composed of heavy and light protein chains encoded at three genomic loci. The IG Kappa (IGK) chain locus consists of two large, inverted segmental duplications. The complexity of the IG loci has hindered use of standard high-throughput methods for characterizing genetic variation within these regions. To overcome these limitations, we use long-read sequencing to create haplotype-resolved IGK assemblies in an ancestrally diverse cohort (n = 36), representing the first comprehensive description of IGK haplotype variation. We identify extensive locus polymorphism, including novel single nucleotide variants (SNVs) and novel structural variants harboring functional IGKV genes. Among 47 functional IGKV genes, we identify 145 alleles, 67 of which were not previously curated. We report inter-population differences in allele frequencies for 10 IGKV genes, including alleles unique to specific populations within this dataset. We identify haplotypes carrying signatures of gene conversion that associate with SNV enrichment in the IGK distal region, and a haplotype with an inversion spanning the proximal and distal regions. These data provide a critical resource of curated genomic reference information from diverse ancestries, laying a foundation for advancing our understanding of population-level genetic variation in the IGK locus.","PeriodicalId":12691,"journal":{"name":"Genes and immunity","volume":"25 4","pages":"297-306"},"PeriodicalIF":5.0,"publicationDate":"2024-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41435-024-00279-2.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141283487","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Osteogenesis imperfecta type 10 and the cellular scaffolds underlying common immunological diseases 10 型成骨不全症和常见免疫疾病的细胞支架。

IF 5 3区医学

Genes and immunity Pub Date : 2024-05-29 DOI: 10.1038/s41435-024-00277-4

Alan Herbert

{"title":"Osteogenesis imperfecta type 10 and the cellular scaffolds underlying common immunological diseases","authors":"Alan Herbert","doi":"10.1038/s41435-024-00277-4","DOIUrl":"10.1038/s41435-024-00277-4","url":null,"abstract":"Osteogenesis imperfecta type 10 (OI10) is caused by loss of function codon variants in the gene SERPINH1 that encodes heat shock protein 47 (HSP47), rather than in a gene specifying bone formation. The HSP47 variants disrupt the folding of both collagen and the endonuclease IRE1α (inositol-requiring enzyme 1α) that splices X-Box Binding Protein 1 (XBP1) mRNA. Besides impairing bone development, variants likely affect osteoclast differentiation. Three distinct biochemical scaffold play key roles in the differentiation and regulated cell death of osteoclasts. These scaffolds consist of non-templated protein modifications, ordered lipid arrays, and protein filaments. The scaffold components are specified genetically, but assemble in response to extracellular perturbagens, pathogens, and left-handed Z-RNA helices encoded genomically by flipons. The outcomes depend on interactions between RIPK1, RIPK3, TRIF, and ZBP1 through short interaction motifs called RHIMs. The causal HSP47 nonsynonymous substitutions occur in a novel variant leucine repeat region (vLRR) that are distantly related to RHIMs. Other vLRR protein variants are causal for a variety of different mendelian diseases. The same scaffolds that drive mendelian pathology are associated with many other complex disease outcomes. Their assembly is triggered dynamically by flipons and other context-specific switches rather than by causal, mendelian, codon variants.","PeriodicalId":12691,"journal":{"name":"Genes and immunity","volume":"25 4","pages":"265-276"},"PeriodicalIF":5.0,"publicationDate":"2024-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141174301","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Machine learning-derived immunosenescence index for predicting outcome and drug sensitivity in patients with skin cutaneous melanoma 用于预测皮肤黑色素瘤患者预后和药物敏感性的机器学习衍生免疫衰老指数

IF 5 3区医学

Genes and immunity Pub Date : 2024-05-29 DOI: 10.1038/s41435-024-00278-3

Linyu Zhu, Lvya Zhang, Junhua Qi, Zhiyu Ye, Gang Nie, Shaolong Leng

{"title":"Machine learning-derived immunosenescence index for predicting outcome and drug sensitivity in patients with skin cutaneous melanoma","authors":"Linyu Zhu, Lvya Zhang, Junhua Qi, Zhiyu Ye, Gang Nie, Shaolong Leng","doi":"10.1038/s41435-024-00278-3","DOIUrl":"10.1038/s41435-024-00278-3","url":null,"abstract":"The functions of immunosenescence are closely related to skin cutaneous melanoma (SKCM). The aim of this study is to uncover the characteristics of immunosenescence index (ISI) to identify novel biomarkers and potential targets for treatment. Firstly, integrated bioinformatics analysis was carried out to identify risk prognostic genes, and their expression and prognostic value were evaluated. Then, we used the computational algorithm to estimate ISI. Finally, the distribution characteristics and clinical significance of ISI in SKCM by using multi-omics analysis. Patients with a lower ISI had a favorable survival rate, lower chromosomal instability, lower somatic copy-number alterations, lower somatic mutations, higher immune infiltration, and sensitive to immunotherapy. The ISI exhibited robust, which was validated in multiple datasets. Besides, the ISI is more effective than other published signatures in predicting survival outcomes for patients with SKCM. Single-cell analysis revealed higher ISI was specifically expressed in monocytes, and correlates with the differentiation fate of monocytes in SKCM. Besides, individuals exhibiting elevated ISI levels could potentially receive advantages from chemotherapy, and promising compounds with the potential to target high ISI were recognized. The ISI model is a valuable tool in categorizing SKCM patients based on their prognosis, gene mutation signatures, and response to immunotherapy.","PeriodicalId":12691,"journal":{"name":"Genes and immunity","volume":"25 3","pages":"219-231"},"PeriodicalIF":5.0,"publicationDate":"2024-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141174296","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Integrated analyses reveal the diagnostic and predictive values of COL5A2 and association with immune environment in Crohn’s disease 综合分析揭示了 COL5A2 的诊断和预测价值以及与克罗恩病免疫环境的关联。

IF 5 3区医学

Genes and immunity Pub Date : 2024-05-24 DOI: 10.1038/s41435-024-00276-5

Tingting Zhong, Xiaoqing Cheng, Qianru Gu, Guoxiang Fu, Yihong Wang, Yujie Jiang, Jiaqi Xu, Zhinong Jiang

{"title":"Integrated analyses reveal the diagnostic and predictive values of COL5A2 and association with immune environment in Crohn’s disease","authors":"Tingting Zhong, Xiaoqing Cheng, Qianru Gu, Guoxiang Fu, Yihong Wang, Yujie Jiang, Jiaqi Xu, Zhinong Jiang","doi":"10.1038/s41435-024-00276-5","DOIUrl":"10.1038/s41435-024-00276-5","url":null,"abstract":"The pathogenesis of Crohn’s disease (CD) involves abnormal immune cell infiltration and dysregulated immune response. Therefore, thorough research on immune cell abnormalities in CD is crucial for improved treatment of this disease. Single-cell RNA sequencing (scRNA-seq) and bulk RNA-seq data of CD were obtained from the Gene Expression Omnibus (GEO) database. Cell-type identification by estimating relative subsets of RNA transcripts (CIBERSORT), weighted gene co-expression network analysis (WGCNA), protein–protein interaction (PPI) networks evaluated the proportion of immune infiltrating cells, constructed co-expression network and identified key genes, respectively. Based on the dataset (GSE134809), 15 cell clusters were defined and labeled as different cell types. Among the 11 modules, the yellow module had the closest relationship with plasma cells (cluster 5). Confirmed using RNA sequencing and IHC assay, the expression of COL5A2 in CD samples was higher than that in control samples. Furthermore, the COL5A2 protein expression remarkably decreased in the group of patients who responded to anti–tumor necrosis factor (TNF) treatments, compared to the non-response group. The comprehensive analyses described here provided novel insight into the landscape of CD-associated immune environment. In addition, COL5A2 were identified as potential diagnostic indicators for CD, as well as promising predictive markers for CD patients.","PeriodicalId":12691,"journal":{"name":"Genes and immunity","volume":"25 3","pages":"209-218"},"PeriodicalIF":5.0,"publicationDate":"2024-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41435-024-00276-5.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141093362","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

TIMP-1 is an activator of MHC-I expression in myeloid dendritic cells with implications for tumor immunogenicity TIMP-1 是骨髓树突状细胞中 MHC-I 表达的激活剂，对肿瘤免疫原性有影响。

IF 5 3区医学

Genes and immunity Pub Date : 2024-05-22 DOI: 10.1038/s41435-024-00274-7

Miriam Langguth, Eleftheria Maranou, Saara A. Koskela, Oskar Elenius, Roosa E. Kallionpää, Eva-Maria Birkman, Otto I. Pulkkinen, Maria Sundvall, Marko Salmi, Carlos R. Figueiredo

{"title":"TIMP-1 is an activator of MHC-I expression in myeloid dendritic cells with implications for tumor immunogenicity","authors":"Miriam Langguth, Eleftheria Maranou, Saara A. Koskela, Oskar Elenius, Roosa E. Kallionpää, Eva-Maria Birkman, Otto I. Pulkkinen, Maria Sundvall, Marko Salmi, Carlos R. Figueiredo","doi":"10.1038/s41435-024-00274-7","DOIUrl":"10.1038/s41435-024-00274-7","url":null,"abstract":"Immune checkpoint therapies (ICT) for advanced solid tumors mark a new milestone in cancer therapy. Yet their efficacy is often limited by poor immunogenicity, attributed to inadequate priming and generation of antitumor T cells by dendritic cells (DCs). Identifying biomarkers to enhance DC functions in such tumors is thus crucial. Tissue Inhibitor of Metalloproteinases-1 (TIMP-1), recognized for its influence on immune cells, has an underexplored relationship with DCs. Our research reveals a correlation between high TIMP1 levels in metastatic melanoma and increased CD8 + T cell infiltration and survival. Network studies indicate a functional connection with HLA genes. Spatial transcriptomic analysis of a national melanoma cohort revealed that TIMP1 expression in immune compartments associates with an HLA-A/MHC-I peptide loading signature in lymph nodes. Primary human and bone-marrow-derived DCs secrete TIMP-1, which notably increases MHC-I expression in classical type 1 dendritic cells (cDC1), especially under melanoma antigen exposure. TIMP-1 affects the immunoproteasome/TAP complex, as seen by upregulated PSMB8 and TAP-1 levels of myeloid DCs. This study uncovers the role of TIMP-1 in DC-mediated immunogenicity with insights into CD8 + T cell activation, providing a foundation for mechanistic exploration and highlighting its potential as a new target for combinatorial immunotherapy to enhance ICT effectiveness.","PeriodicalId":12691,"journal":{"name":"Genes and immunity","volume":"25 3","pages":"188-200"},"PeriodicalIF":5.0,"publicationDate":"2024-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41435-024-00274-7.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141081226","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

HER2-targeting CAR-T cells show highly efficient anti-tumor activity against glioblastoma both in vitro and in vivo HER2靶向CAR-T细胞在体外和体内对胶质母细胞瘤都显示出高效的抗肿瘤活性。

IF 5 3区医学

Genes and immunity Pub Date : 2024-05-03 DOI: 10.1038/s41435-024-00275-6

Xueying Li, Lifen Zhao, Wenzhe Li, Peng Gao, Nianzhu Zhang

{"title":"HER2-targeting CAR-T cells show highly efficient anti-tumor activity against glioblastoma both in vitro and in vivo","authors":"Xueying Li, Lifen Zhao, Wenzhe Li, Peng Gao, Nianzhu Zhang","doi":"10.1038/s41435-024-00275-6","DOIUrl":"10.1038/s41435-024-00275-6","url":null,"abstract":"Glioblastoma (GBM) is the most common and aggressive malignant primary brain tumor in adults. Current treatment options for GBM include surgical resection, radiation, and chemotherapy, which predominantly slow cancer growth and reduce symptoms, resulting in a 5-year survival rate of no more than 10%. Chimeric antigen receptor (CAR) T-cell therapy is a new class of cellular immunotherapy that has made great progress in treating malignant tumors. Human epidermal growth factor receptor 2 (HER2) is overexpressed in GBM and may provide a potential therapeutic target for GBM treatment. In this study, we constructed third-generation CAR-T cells targeting the HER2 antigen in GBM. HER2-CAR-T cells showed effective anti-tumor activity both in vitro and in vivo. Furthermore, HER2-specific CAR-T cells exhibited strong cytotoxicity and cytokine-secreting abilities against GBM cells in vitro. Anti-HER2 CAR-T cells also exhibited increased cytotoxicity with increasing effector-to-target ratios. Anti-HER2 CAR-T cells delivered via peritumoral injection successfully stunted tumor progression in vivo. Moreover, peritumoral intravenous administration of anti-HER2 CAR-T cells resulted in therapeutic improvement against GBM cells compared with intravenous administration. In conclusion, our study shows that HER2 CAR-T cells represent an emerging immunotherapy for treating GBM.","PeriodicalId":12691,"journal":{"name":"Genes and immunity","volume":"25 3","pages":"201-208"},"PeriodicalIF":5.0,"publicationDate":"2024-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41435-024-00275-6.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140851071","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0