scImmOmics: a manually curated resource of single-cell multi-omics immune data

Nucleic Acids Research, Journal Year: 2024, Volume and Issue: 53(D1), P. D1162 - D1172

Published: Nov. 4, 2024

Single-cell sequencing technology has enabled the discovery and characterization of subpopulations immune cells with unique functions, which is critical for revealing responses under healthy or disease conditions. Efforts have been made to collect curate single-cell RNA (scRNA-seq) data, yet an immune-specific multi-omics atlas harmonized metadata still lacking. Here, we present scImmOmics (https://bio.liclab.net/scImmOmics/home), a manually curated database constructed based on high-quality known cell labels. Currently, documents >2.9 million cell-type labeled derived from seven technologies, involving 131 types, 47 tissues 4 species. To ensure data consistency, standardized nomenclature types presented them in hierarchical tree structure clearly describe lineage relationships within system. also provides comprehensive regulatory information, including T-cell/B-cell receptor clonotype cell-specific information (e.g. gene/chromatin accessibility/protein/transcription factor states cell-to-cell communication co-expression networks) cytokines. Collectively, valuable platform unraveling heterogeneity diversity elucidating specific mechanisms at level.

Language: Английский

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The characterization of tumor immune microenvironment after neoadjuvant immunotherapy in head and neck squamous cell cancer using multiplex immunohistochemistry

Oral Oncology, Journal Year: 2025, Volume and Issue: 161, P. 107151 - 107151

Published: Jan. 1, 2025

Language: Английский

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Disrupting EDEM3‐induced M2‐like macrophage trafficking by glucose restriction overcomes resistance to PD‐1/PD‐L1 blockade

Clinical and Translational Medicine, Journal Year: 2025, Volume and Issue: 15(1)

Published: Jan. 1, 2025

Immunotherapy is beneficial for some colorectal cancer (CRC) patients, but immunosuppressive networks limit its effectiveness. Cancer-associatedfibroblasts (CAFs) are significant in immune escape and resistance toimmunotherapy, emphasizing the urgent need new treatment strategies. Flow cytometric, Western blotting, proteomics analysis, analysis of public database data, genetically modified cell line models, T coculture, crystal violetstaining, ELISA, metabonomic clinical tumour samples were conducted to assess role EDEM3 itsmolecular mechanisms. We evaluated theeffects FMD plus 2-DG on antitumour immunity using multipleximmunofluorescence, flow cytometry, cytokine profiling, TUNEL assays, xenografttumours, vivo studies. show thatCAFs upregulate PD-L1 glycosylation contribute evasion byglycosyltransferase EDEM3. Additionally, plays a immunityduring progression. However, EDEM3-mediated upregulation expression underpins PD-1/PD-L1 blockade vivo. This finding contradictsthe previous trend that positive indicates strong responseto blockade. Mechanistically, high-EDEM3 facilitates M2-like blockade.Mechanistically, polarizationand chemotactic migration macrophages, which enriched theperipheral region tumours compared thecore region, precluding access CD8+ cells tumourfoci. Furthermore, we predominantly activates recruited macrophagesvia glucose metabolism-dependent mechanism. Manipulationof utilization by fasting-mimicking diet(FMD) treatmentsynergistically with PD-1 antibody elicits potent activity byeffectively decreasing glycosylated expression, augmenting CD8+effector infiltration activation while concurrently reducing infiltration.TheCAFs-EDEM3-M2-like macrophage axis critical promotingimmunotherapy resistance. Our study suggests blocking EDEM3-induced macro phage trafficking promising effective strategy overcomeresistance checkpoint therapy offeringhope improved outcomes. Cancer-associated fibroblasts can enhance through glycosyltransferase EDEM3, contributing during recruit macrophages via Blocking antagonizes recruiting polarizing synergistically improve anticancer immunity.

Language: Английский

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Navigating the immune landscape with plasma cells: A pan‐cancer signature for precision immunotherapy

BioFactors, Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 4, 2024

Abstract Immunotherapy has revolutionized cancer treatment; however, predicting patient response remains a significant challenge. Our study identified novel plasma cell signature, Plasma cell.Sig, through pan‐cancer single‐cell RNA sequencing analysis, which predicts outcomes to immunotherapy with remarkable accuracy. The signature was developed using rigorous machine learning algorithms and validated across multiple cohorts, demonstrating superior predictive power an area under the curve (AUC) exceeding 0.7. Notably, low‐risk group, as classified by exhibited enriched immune infiltration heightened tumor immunogenicity, indicating enhanced responsiveness immunotherapy. Conversely, high‐risk group showed reduced activity potential mechanisms of evasion. These findings not only enhance understanding intrinsic extrinsic landscapes within microenvironment but also pave way for more precise, biomarker‐guided approaches in oncology.

Language: Английский

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IDO1 inhibitor enhances the effectiveness of PD-1 blockade in microsatellite stable colorectal cancer by promoting macrophage pro-inflammatory phenotype polarization

Cancer Immunology Immunotherapy, Journal Year: 2025, Volume and Issue: 74(2)

Published: Jan. 3, 2025

Microsatellite stable (MSS) colorectal cancer (CRC) is a subtype of CRC that generally exhibits resistance to immunotherapy, particularly immune checkpoint inhibitors such as PD-1 blockade. This study investigates the effects and underlying mechanisms combining blockade with IDO1 inhibition in MSS CRC. Bioinformatics analyses TCGA-COAD TCGA-READ cohorts revealed significantly elevated expression tumors, correlating tumor mutation burden across TCGA datasets. In vivo experiments demonstrated combination reduced growth increased cell infiltration, pro-inflammatory macrophages CD8+ T cells. knockdown lines impaired tolerance interferon-γ apoptosis vitro, which were rescued by application kynurenine, end product IDO1. enhanced effectiveness therapy vivo. cells promoted macrophage polarization phagocytic activity associated upregulation JAK2-STAT3-IL6 signaling pathway. These findings highlight role modulating microenvironment suggest could enhance therapeutic efficacy promoting infiltration through

Language: Английский

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Enhancing immunotherapy efficacy in oral cancer through AKB-9778-mediated vascular normalization

International Immunopharmacology, Journal Year: 2025, Volume and Issue: 148, P. 114133 - 114133

Published: Jan. 28, 2025

Language: Английский

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Advancements in cellular immunotherapy: overcoming resistance in lung and colorectal cancer

Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 16

Published: Feb. 5, 2025

Immunotherapy has revolutionized cancer treatment, offering hope for patients with otherwise treatment-resistant tumors. Among the most promising approaches are cellular therapies, particularly chimeric antigen receptor T-cell (CAR-T) therapy, which shown remarkable success in hematologic malignancies. However, application of these therapies to solid tumors, such as lung and colorectal cancers, faced significant challenges. Tumor resistance mechanisms—ranging from immune evasion, loss, checkpoint upregulation, tumor microenvironment immunosuppression—remain major obstacles. This mini-review highlights latest advancements immunotherapy, a focus on addresses mechanisms that hinder their effectiveness cancers. We examine evolution CAR-T cell well potential engineered natural killer (NK) cells macrophages treatment. The review also explores cutting-edge strategies aimed at overcoming resistance, including combination gene editing technologies, nanotechnology targeted drug delivery. By discussing molecular, cellular, microenvironmental factors contributing we aim provide comprehensive overview how challenges can be overcome, paving way more effective, personalized immunotherapies

Language: Английский

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Multi-omics analyses reveal biological and clinical insights in recurrent stage I non-small cell lung cancer

Nature Communications, Journal Year: 2025, Volume and Issue: 16(1)

Published: Feb. 10, 2025

Post-operative recurrence rates of stage I non-small cell lung cancer (NSCLC) range from 20% to 40%. Nonetheless, the molecular mechanisms underlying hitherto remain largely elusive. Here, we generate genomic, epigenomic and transcriptomic profiles paired tumors adjacent tissues 122 NSCLC patients, among which 57 patients develop after surgery during follow-up. Integrated analyses illustrate that presence predominantly solid or micropapillary histological subtypes, increased genomic instability, APOBEC-related signature are associated with recurrence. Furthermore, TP53 missense mutation in DNA-binding domain could contribute shorter time DNA hypomethylation is pronounced recurrent NSCLC, PRAME significantly hypomethylated overexpressed gene adenocarcinoma (LUAD). Mechanistically, at TEAD1 binding site facilitates transcriptional activation PRAME. Inhibition restrains tumor metastasis via downregulation epithelial–mesenchymal transition-related genes. We also identify enrichment AT2 cells higher copy number variation burden, exhausted CD8 + T Macro_SPP1, along reduced interaction between immune cells, essential for formation ecosystem LUAD. Finally, multi-omics clustering stratify into 4 subclusters varying risk subcluster-specific therapeutic vulnerabilities. Collectively, this study constitutes a promising resource enabling insights biological clinical management post-operative NSCLC. The poorly understood. authors do profiling normal finding processes type proportions

Language: Английский

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Tumor Metastasis: Mechanistic Insights and Therapeutic Intervention

MedComm – Oncology, Journal Year: 2025, Volume and Issue: 4(1)

Published: Feb. 17, 2025

ABSTRACT Metastasis remains a leading cause of cancer‐related deaths, defined by complex, multi‐step process in which tumor cells spread and form secondary growths distant tissues. Despite substantial progress understanding metastasis, the molecular mechanisms driving this development effective therapies remain incompletely understood. Elucidating pathways governing metastasis is essential for discovery innovative therapeutic targets. The rapid advancements sequencing technologies expansion biological databases have significantly deepened our drivers associated drug resistance. This review focuses on particularly roles genetic mutations, epigenetic changes, post‐translational modifications progression. We also examine how microenvironment influences metastatic behavior explore emerging strategies, including targeted immunotherapies. Finally, we discuss future research directions, stressing importance novel treatment approaches personalized strategies to overcome improve patient outcomes. By integrating contemporary insights into basis innovation, provides comprehensive framework guide clinical cancer.

Language: Английский

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Predicting immunotherapy prognosis and targeted therapy sensitivity of colon cancer based on a CAF-related molecular signature

Scientific Reports, Journal Year: 2025, Volume and Issue: 15(1)

Published: Feb. 21, 2025

Language: Английский

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