Prognostic signatures of sphingolipids: Understanding the immune landscape and predictive role in immunotherapy response and outcomes of hepatocellular carcinoma

Frontiers in Immunology, Год журнала: 2023, Номер 14

Опубликована: Март 17, 2023

Hepatocellular carcinoma (HCC) is a complex disease with poor outlook for patients in advanced stages. Immune cells play an important role the progression of HCC. The metabolism sphingolipids functions both tumor growth and immune infiltration. However, little research has focused on using sphingolipid factors to predict HCC prognosis. This study aimed identify key genes (SPGs) develop reliable prognostic model based these genes.The TCGA, GEO, ICGC datasets were grouped SPGs obtained from InnateDB portal. A gene signature was created by applying LASSO-Cox analysis evaluating it Cox regression. validity verified GEO datasets. microenvironment (TME) examined ESTIMATE CIBERSORT, potential therapeutic targets identified through machine learning. Single-cell sequencing used examine distribution within TME. Cell viability migration tested confirm SPGs.We 28 that have impact survival. Using clinicopathological features 6 genes, we developed nomogram high- low-risk groups found distinct characteristics response drugs. Unlike CD8 T cells, M0 M2 macrophages be highly infiltrated TME high-risk subgroup. High levels good indicator immunotherapy. In cell function experiments, SMPD2 CSTA enhance survival Huh7 while silencing increased sensitivity lapatinib.The presents six-gene can aid clinicians choosing personalized treatments patients. Furthermore, uncovers connection between sphingolipid-related microenvironment, offering novel approach By focusing crucial like CSTA, efficacy anti-tumor therapy cells.

Язык: Английский

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Extracellular vesicles in nanomedicine and regenerative medicine: A review over the last decade

Bioactive Materials, Год журнала: 2024, Номер 36, С. 126 - 156

Опубликована: Март 2, 2024

Small extracellular vesicles (sEVs) are known to be secreted by a vast majority of cells. These sEVs, specifically exosomes, induce specific cell-to-cell interactions and can activate signaling pathways in recipient cells through fusion or interaction. nanovesicles possess several desirable properties, making them ideal for regenerative medicine nanomedicine applications. properties include exceptional stability, biocompatibility, wide biodistribution, minimal immunogenicity. However, the practical utilization particularly clinical settings at large scale, is hindered expensive procedures required their isolation, limited circulation lifetime, suboptimal targeting capacity. Despite these challenges, sEVs have demonstrated remarkable ability accommodate various cargoes found extensive applications biomedical sciences. To overcome limitations broaden potential applications, researchers should strive deepen understanding current loading, characterization techniques. Additionally, acquiring fundamental knowledge about origins employing state-of-the-art methodologies expand research scope. This review provides comprehensive overview exosome-based strategies diverse domains, encompassing cancer therapy, immunotherapy, biomarker Furthermore, we emphasize immense exosomes medicine.

Язык: Английский

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Reprogramming of Treg cells in the inflammatory microenvironment during immunotherapy: a literature review

Frontiers in Immunology, Год журнала: 2023, Номер 14

Опубликована: Сен. 11, 2023

Regulatory T cells (Treg), as members of CD4+ cells, have garnered extensive attention in the research tumor progression. Treg function inhibiting immune effector preventing tissue damage, and suppressing inflammation. Under stimulation inflammatory microenvironment (IM), reprogramming enhances their suppression responses, ultimately promoting escape or Reducing number IM lowering activity while reprogramming, can help promote body's anti-tumor responses. This review introduces a mechanism IM; discusses regulation on The control response to immunotherapy are analyzed countermeasures proposed. work will provide foundation for downregulating immunosuppressive role environment future immunotherapy.

Язык: Английский

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The integrated single-cell analysis developed an immunogenic cell death signature to predict lung adenocarcinoma prognosis and immunotherapy

Aging, Год журнала: 2023, Номер 15(19), С. 10305 - 10329

Опубликована: Окт. 4, 2023

Background: Research on immunogenic cell death (ICD) in lung adenocarcinoma (LUAD) has been relatively limited. This study aims to create ICD-related signatures for accurate survival prognosis prediction LUAD patients, addressing the challenge of lacking reliable early prognostic indicators this type cancer. Methods: Using single-cell RNA sequencing (scRNA-seq) analysis, ICD activity cells was calculated by AUCell algorithm, divided into high- and low-ICD groups according median values, key regulatory genes were identified through differential these integrated TCGA data construct using LASSO COX regression multi-dimensional analysis terms prognosis, immunotherapy, tumor microenvironment (TME), mutational landscape. Results: The constructed signature reveals a pronounced disparity between low-risk patients. statistical discrepancies times among patients from both GEO databases further corroborate observation. Additionally, heightened levels immune infiltration expression are evidenced group, suggesting potential benefit immunotherapeutic interventions pivotal risk-associated tissue samples assessed utilizing qRT-PCR, thereby unveiling PITX3 as plausible therapeutic target context LUAD. Conclusions: Our provide help predicting immunotherapy some extent guide clinical treatment

Язык: Английский

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Current research status of tumor cell biomarker detection

Microsystems & Nanoengineering, Год журнала: 2023, Номер 9(1)

Опубликована: Окт. 5, 2023

Abstract With the annual increases in morbidity and mortality rates of tumors, use biomarkers for early diagnosis real-time monitoring tumor cells is great importance. Biomarkers used cell detection body fluids include circulating cells, nucleic acids, protein markers, extracellular vesicles. Among them, DNA, exosomes have high potential prediction, diagnosis, prognosis diseases due to large amount valuable information on characteristics evolution; addition, situ telomerase miRNA living has been topic extensive research understand development real time. Various techniques, such as enzyme-linked immunosorbent assays, immunoblotting, mass spectrometry, widely these markers. markers based electrochemical biosensors fluorescence signal analysis highly preferred because its sensitivity, rapid portable operation. Herein, we summarize recent progress using biosensors, outline current status discuss technical challenges their practical clinical application provide a reference new marker methods.

Язык: Английский

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The Landscape of Exosomes Biogenesis to Clinical Applications

International Journal of Nanomedicine, Год журнала: 2024, Номер Volume 19, С. 3657 - 3675

Опубликована: Апрель 1, 2024

Abstract: Exosomes are extracellular vesicles that originate from various cells and mediate intercellular communication, altering the behavior or fate of recipient cells. They carry diverse macromolecules, such as lipids, proteins, carbohydrates, nucleic acids. Environmental stressors can change exosomal contents many cells, making them useful for diagnosing chronic disorders, especially neurodegenerative, cardiovascular, cancerous, diabetic diseases. Moreover, exosomes be engineered therapeutic agents to modulate disease processes. State-of-art techniques employed separate including ultracentrifugation, size-exclusion chromatography immunoaffinity. However, modern technologies aqueous two-phase system well microfluidics gaining attention in recent years. The article highlighted composition, biogenesis, implications exosomes, standard novel methods isolating applying biomarkers cargo carriers. Keywords: Exosomes, vesicles, biomarkers, carriers, separation

Язык: Английский

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Immunoregulatory functions and therapeutic potential of natural killer cell-derived extracellular vesicles in chronic diseases

Frontiers in Immunology, Год журнала: 2024, Номер 14

Опубликована: Янв. 3, 2024

Extracellular vesicles (EVs) have been proven to play a significant immunoregulatory role in many chronic diseases, such as cancer and immune disorders. Among them, EVs derived from NK cells are an essential component of the cell functions. These demonstrated carry variety toxic proteins nucleic acids therapeutic diseases like malignancies, liver fibrosis, lung injury. However, natural NK-derived (NKEVs) certain limitations disease treatment, low yield poor targeting. Concurrently, exhibit characteristics memory-like cells, which stronger proliferative capacity, increased IFN-γ production, enhanced cytotoxicity, making them more advantageous for treatment. Recent research has shifted its focus towards engineered extracellular their potential improve efficiency, specificity, safety treatments. In this review, we will discuss latest advancements therapy. Specifically, compare different cellular sources NKEVs explore current status prospects cell-derived NKEVs.

Язык: Английский

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Glycogen metabolism-mediated intercellular communication in the tumor microenvironment influences liver cancer prognosis

Oncology Research Featuring Preclinical and Clinical Cancer Therapeutics, Год журнала: 2024, Номер 32(3), С. 563 - 576

Опубликована: Янв. 1, 2024

Glycogen metabolism plays a key role in the development of hepatocellular carcinoma (HCC), but function glycogen genes tumor microenvironment (TME) is still to be elucidated. Single-cell RNA-seq data were obtained from ten HCC samples totaling 64,545 cells, and 65 analyzed by nonnegative matrix factorization (NMF). The prognosis immune response new TME cell clusters predicted using immunotherapy cohorts public databases. single-cell analysis was divided into fibroblasts, NT T macrophages, endothelial B which separately gene annotation. Pseudo-temporal trajectory demonstrated temporal differentiation different subtype clusters. Cellular communication revealed extensive interactions between cells with metabolizing cell-related subtypes SCENIC transcription factors upstream metabolism. In addition, found enriched expression CAF subtypes, CD8 depleted, M1, M2 types. Bulk-seq showed prognostic significance metabolism-mediated HCC, while significant cohort patients treated checkpoint blockade (ICB), especially for CAFs, macrophages. summary, our study reveals first time that mediates intercellular elucidating anti-tumor mechanisms responses

Язык: Английский

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Revealing the role of regulatory T cells in the tumor microenvironment of lung adenocarcinoma: a novel prognostic and immunotherapeutic signature

Frontiers in Immunology, Год журнала: 2023, Номер 14

Опубликована: Авг. 21, 2023

Regulatory T cells (Tregs), are a key class of cell types in the immune system. In tumor microenvironment (TME), presence Tregs has important implications for response and development. Relatively little is known about role lung adenocarcinoma (LUAD).Tregs were identified using but single-cell RNA sequencing (scRNA-seq) analysis interactions between other TME investigated. Next, we used multiple bulk RNA-seq datasets to construct risk models based on marker genes explored differences prognosis, mutational landscape, infiltration immunotherapy high- low-risk groups, finally, qRT-PCR function experiments performed validate model genes.The cellchat showed that MIF-(CD74+CXCR4) pairs play interaction with subpopulations, Tregs-associated signatures (TRAS) could well classify LUAD cohorts into groups. Immunotherapy may offer greater potential benefits group, as indicated by their superior survival, increased cells, heightened expression checkpoints. Finally, experiment verified LTB PTTG1 relatively highly expressed cancer tissues, while PTPRC was paracancerous tissues. Colony Formation assay confirmed knockdown reduced proliferation ability cells.TRAS constructed scRNA-seq distinguish patient subgroups, which provide assistance clinical management patients.

Язык: Английский

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Combining single-cell sequencing and spatial transcriptome sequencing to identify exosome-related features of glioblastoma and constructing a prognostic model to identify BARD1 as a potential therapeutic target for GBM patients

Frontiers in Immunology, Год журнала: 2023, Номер 14

Опубликована: Авг. 31, 2023

Glioblastoma (GBM) is a malignant primary brain tumor. This study focused on exploring the exosome-related features of glioblastoma to better understand its cellular composition and molecular characteristics.Single-cell RNA sequencing (scRNA-seq) spatial transcriptome (stRNA-seq) were used analyze heterogeneity glioblastomas. After data integration, cell clustering, annotation, five algorithms calculate scores for genes(ERGs). Cell trajectory analysis intercellular communication performed explore patterns. Spatial analyzed validate findings. To further utilize aid in clinical decision-making, prognostic model was constructed using GBM's bulk RNA-seq.Different subpopulations observed GBM, with Monocytes/macrophages cells tumor samples showing higher scores. identifying differentially expressed ERGs cells, pseudotime revealed status during development. Intercellular highlighted signaling pathways ligand-receptor interactions. confirmed high expression gene core region. A based six shown be predictive overall survival immunotherapy outcome GBM patients. Finally, results scRNA-seq modeling as well series function experiments, BARD1 identified novel target treatment GBM.This provides comprehensive understanding both stRNA-seq, exhibiting stronger Monocytes/macrophages. In terms data, highly scored also concentrated RNA-seq, patients index exhibited an immunosuppressive microenvironment, which accompanied by worse prognosis outcomes. Prognostic models are expected independent indicators patients, potential implications personalized strategies GBM. Knockdown lines reduces invasive value-added capacity thus BARD1-positively expressing risk factor

Язык: Английский

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