Metabolic reprogramming in tumor immune microenvironment: Impact on immune cell function and therapeutic implications

Cancer Letters, Год журнала: 2024, Номер 597, С. 217076 - 217076

Опубликована: Июнь 19, 2024

Understanding of the metabolic reprogramming has revolutionized our insights into tumor progression and potential treatment. This review concentrates on aberrant pathways in cancer cells within microenvironment (TME). Cancer differ from normal their processing glucose, amino acids, lipids order to adapt heightened biosynthetic energy needs. These shifts, which crucially alter lactic acid, acid lipid metabolism, affect not only cell proliferation but also TME dynamics. explores various immune TME. From a therapeutic standpoint, targeting these alterations represents novel treatment strategy. discusses approaches regulation metabolism different nutrients influencing enhance response. In summary, this summarizes its as target for innovative strategies, offering fresh perspectives

Язык: Английский

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Current approaches to develop “off-the-shelf” chimeric antigen receptor (CAR)-T cells for cancer treatment: a systematic review

Experimental Hematology and Oncology, Год журнала: 2023, Номер 12(1)

Опубликована: Авг. 21, 2023

Chimeric antigen receptor (CAR)-T cell therapy is one of the most promising advances in cancer treatment. It based on genetically modified T cells to express a CAR, which enables recognition specific tumour interest. To date, CAR-T therapies approved for commercialisation are designed treat haematological malignancies, showing impressive clinical efficacy patients with relapsed or refractory advanced-stage tumours. However, since they all use patient´s own as starting material (i.e. autologous use), have important limitations, including manufacturing delays, high production costs, difficulties standardising preparation process, and failures due patient dysfunction. Therefore, many efforts currently being devoted contribute development safe effective allogeneic use, should be overcome risks entail: immune rejection graft-versus-host disease (GvHD). This systematic review brings together wide range different approaches that been studied achieve discuss advantages disadvantages every strategy. The methods were classified two major categories: those involving extra genetic modifications, addition CAR integration, relying selection alternative sources/subpopulations γδ cells, induced pluripotent stem (iPSCs), umbilical cord blood memory subpopulations, virus-specific cytokine-induced killer cells). We observed that, although modification widely used approach, new combining both emerged. more preclinical research needed determine appropriate strategy bring this antitumour setting.

Язык: Английский

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α-KG inhibits tumor growth of diffuse large B-cell lymphoma by inducing ROS and TP53-mediated ferroptosis

Cell Death Discovery, Год журнала: 2023, Номер 9(1)

Опубликована: Июнь 12, 2023

Abstract Metabolic reprogramming is a hallmark of human malignancies. Dysregulation glutamine metabolism essential for tumorigenesis, microenvironment remodeling, and therapeutic resistance. Based on the untargeted metabolomics sequencing, we identified that metabolic pathway was up-regulated in serum patients with primary DLBCL. High levels were associated inferior clinical outcomes, indicative prognostic value In contrast, derivate alpha-ketoglutarate (α-KG) negatively correlated invasiveness features DLBCL patients. Further, found treatment cell-permeable derivative α-KG, known as DM-αKG, significantly suppressed tumor growth by inducing apoptosis non-apoptotic cell death. Accumulation a-KG promoted oxidative stress double-hit lymphoma (DHL), which depended malate dehydrogenase 1 (MDH1)-mediated 2-hydroxyglutarate (2-HG) conversion. reactive oxygen species (ROS) contributed to ferroptosis induction promoting lipid peroxidation TP53 activation. particular, overexpression derived from DNA damage, further leading activation ferroptosis-related pathways. Our study demonstrated importance progression highlighted potential application α-KG novel strategy DHL

Язык: Английский

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Single-cell and spatial transcriptomics reveal a high glycolysis B cell and tumor-associated macrophages cluster correlated with poor prognosis and exhausted immune microenvironment in diffuse large B-cell lymphoma

Biomarker Research, Год журнала: 2024, Номер 12(1)

Опубликована: Июнь 5, 2024

Abstract Background Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous malignancy characterized by varied responses to treatment and prognoses. Understanding the metabolic characteristics driving DLBCL progression crucial for developing personalized therapies. Methods This study utilized multiple omics technologies including single-cell transcriptomics ( n = 5), bulk 966), spatial 10), immunohistochemistry 34), immunofluorescence 20) elucidate features of highly malignant cells tumor-associated macrophages (TAMs), along with their associated tumor microenvironment. Metabolic pathway analysis facilitated scMetabolism, integrated via hdWGCNA, identified glycolysis genes correlating malignancy, prognostic value STMN1, ENO1, PKM , CDK1 ) TAMs were verified. Results High-glycolysis tissues exhibited an immunosuppressive microenvironment abundant IFN_TAMs (CD68 + CXCL10 PD-L1 diminished CD8 T cell infiltration. Glycolysis positively correlated degree. high activity closely communicating high-malignancy within datasets. The score, evaluated seven genes, emerged as independent factor HR 1.796, 95% CI : 1.077–2.995, p 0.025 2.631, 1.207–5.735, 0.015) poor survival < 0.05) in DLBCL. Immunohistochemical validation markers underscored Conclusions underscores significance modulation immune represent potential therapeutic targets

Язык: Английский

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Molecular Subtyping and Survival Analysis of Osteosarcoma Reveals Prognostic Biomarkers and Key Canonical Pathways

Cancers, Год журнала: 2023, Номер 15(7), С. 2134 - 2134

Опубликована: Апрель 4, 2023

Osteosarcoma (OS) is a common bone malignancy in children and adolescents. Although histological subtyping followed by improved OS treatment regimens have helped achieve favorable outcomes, lack of understanding the molecular subtypes remains challenge to characterize its genetic heterogeneity subsequently identify diagnostic prognostic biomarkers for developing effective treatments. In present study, global analysis DNA methylation, mRNA miRNA gene expression patient samples were correlated with their clinical characteristics. The mucin family genes, MUC6, MUC12, MUC4, found be highly mutated patients. Results revealed enrichment pathways including Wnt signaling, Calcium PI3K-Akt signaling tumors. Survival analyses showed that levels several genes such as RAMP1, CRIP1, CORT, CHST13, DDX60L, miRNAs lncRNAs associated survival Molecular using Cluster-Of-Clusters Analysis (COCA) mRNA, lncRNA, expression; methylation; mutation data from TARGET dataset two distinct subtypes, each distinctive profile. Between three upregulated POP4, HEY1, CERKL, seven downregulated CEACAM1, ABLIM1, LTBP2, ISLR, LRRC32, PTPRF, GPX3, metastasis differentially regulated. Thus, results provide strong basis classification patients could used develop better strategies.

Язык: Английский

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Prediction significance of autophagy-related genes in survival probability and drug resistance in diffuse large B-cell lymphoma

Aging, Год журнала: 2024, Номер unknown

Опубликована: Янв. 17, 2024

Background/Aims: Diffuse large B-cell lymphoma (DLBCL), the most common subtype of non-Hodgkin lymphoma, has significant prognostic heterogeneity. This study aimed to generate a prediction model based on autophagy-related genes for DLBCL patients. Methods: Utilizing bioinformatics techniques, we analyzed clinical information and transcriptome data patients from Gene Expression Omnibus (GEO) database. Through unsupervised clustering, identified new molecular subtypes pinpointed differentially expressed (DEGs) between these subtypes. Based DEGs, was constructed using Cox Lasso regression. The effectiveness, accuracy, utility this were assessed numerous independent validation cohorts, survival analyses, receiver operating characteristic (ROC) curves, multivariate regression analysis, nomograms, calibration curves. Moreover, functional immune cell infiltration, drug sensitivity analysis performed. Results: with different characterizations (age, subtypes, ECOG scores, stages) showed expression features genes. eight (ADD3, IGFBP3, TPM1, LYZ, AFDN, DNAJC10, GLIS3, CCDC102A). nomogram overall incorporated risk level, stage, showing excellent agreement observed predicted outcomes. Differences noted in proportions cells (native B cells, Treg CD8+ T cell, CD4+ memory activated gamma delta macrophages M1, resting mast cells) high-risk low-risk groups. LYZ ADD3 exhibited correlations resistance chemotherapeutic drugs. Conclusions: established novel assessment profile characteristics patients, explored infiltration resistance, which may guide precise individualized immunochemotherapy regimens.

Язык: Английский

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Amino Acid Metabolism-Related Gene Kynureninase (KYNU) as a Prognostic Predictor and Regulator of Diffuse Large B-Cell Lymphoma

Biochemical Genetics, Год журнала: 2025, Номер unknown

Опубликована: Фев. 11, 2025

Язык: Английский

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MicroRNAs in Diffuse Large B-Cell Lymphoma (DLBCL): Biomarkers with Prognostic Potential

Cancers, Год журнала: 2025, Номер 17(8), С. 1300 - 1300

Опубликована: Апрель 12, 2025

Background/Objectives: The heterogeneity of diffuse large B-cell lymphoma (DLBCL) based on differences in both genetic and epigenetic factors contributes to the dynamics tumor growth efficacy cytoreductive therapy, as well considerably affecting disease prognosis. This study aimed detect microRNAs (miRNAs) capable improving prognostic accuracy DLBCL patients. Methods: We performed miRNA sequencing bone marrow (BM) samples collected from Next, expression levels miRNAs lymph node (LN) (n = 43) BM 70) were analyzed by real-time RT-PCR group Results: It was found that miRNA-10b, -100, -125a, -125b, -126, -143, -23a let-7a statistically significantly reduced patients who had a poor prognosis compared with favorable (p < 0.05). Kaplan–Meier survival analysis demonstrated upregulated miRNA-23a, miRNA-125a, miRNA-100 associated better overall A significant elevation miRNA-151a, miRNA-148b miRNA-192 observed for without involvement non-cancerous blood (NCBD) Statistically upregulation PD-L1, TIMP1, TOP2A, TP53 comparison NCBD Conclusions: shown be potential prognostically biomarkers Changes miRNA-148b, miRNA-192, reflect alterations morphological or immunophenotypic signs DLBCL-related pathology.

Язык: Английский

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Metabolic Reprogramming and Potential Therapeutic Targets in Lymphoma

International Journal of Molecular Sciences, Год журнала: 2023, Номер 24(6), С. 5493 - 5493

Опубликована: Март 13, 2023

Lymphoma is a heterogeneous group of diseases that often require their metabolism program to fulfill the demand cell proliferation. Features in lymphoma cells include high glucose uptake, deregulated expression enzymes related glycolysis, dual capacity for glycolytic and oxidative metabolism, elevated glutamine fatty acid synthesis. These aberrant metabolic changes lead tumorigenesis, disease progression, resistance chemotherapy. This reprogramming, including glucose, nucleic acid, amino dynamic process caused not only by genetic epigenetic changes, but also microenvironment affected viral infections. Notably, some critical metabolites may play vital roles lymphomagenesis progression. Recent studies have uncovered pathways might clinical impacts on diagnosis, characterization, treatment subtypes. However, determining relevance biomarkers therapeutic targets still challenging. In this review, we systematically summarize current reprogramming lymphoma, mainly focus disorders acids, lipid metabolisms, as well dysregulation molecules pathways, oncometabolites, potential biomarkers. We then discuss strategies directly or indirectly those targets. Finally, prospect future directions reprogramming.

Язык: Английский

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Specific mortality in patients with diffuse large B-cell lymphoma: a retrospective analysis based on the surveillance, epidemiology, and end results database

European journal of medical research, Год журнала: 2024, Номер 29(1)

Опубликована: Апрель 20, 2024

The full potential of competing risk modeling approaches in the context diffuse large B-cell lymphoma (DLBCL) patients has yet to be fully harnessed. This study aims address this gap by developing a sophisticated model specifically designed predict specific mortality DLBCL patients.

Язык: Английский

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