Radiotherapy-induced alterations in tumor microenvironment: metabolism and immunity

Frontiers in Cell and Developmental Biology, Год журнала: 2025, Номер 13

Опубликована: Апрель 28, 2025

Tumor metabolism plays a pivotal role in shaping immune responses within the tumor microenvironment influencing progression, evasion, and efficacy of cancer therapies. Radiotherapy has been shown to impact both modulation, often inducing activation through damage-associated molecular patterns STING pathway. In this study, we analyse particular characteristics tumour metabolic its effect on microenvironment. We also review changes that are induced by radiotherapy, with focus sensitisation effects radiotherapy. Our aim is contribute development research ideas field radiotherapy metabolic-immunological studies.

Язык: Английский

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Harnessing nutrient scarcity for enhanced CAR-T-cell potency and safety in solid tumors

Cellular and Molecular Immunology, Год журнала: 2025, Номер unknown

Опубликована: Май 8, 2025

Abstract Despite significant advancements, the effectiveness of chimeric antigen receptor (CAR)-T-cell-based therapies in solid tumors remains limited. Key challenges include on-target effects, off-tumor toxicity and reduced CAR-T-cell function within tumor microenvironment, which is often characterized by metabolic stress triggered factors such as amino acid scarcity. Activating transcription factor-4 (ATF4) its upstream regulator GCN2 play crucial roles reprogramming functionality CD4 + CD8 T cells. ATF4 can be activated various cellular signals, including deprivation. While activation may associated with T-cell dysfunction, role adaptation presents an opportunity for therapeutic intervention—particularly where exhaustion a major challenge. In this study, we developed strategy to harness GCN2‒ATF4 axis CAR-T We employed acid-dependent inducible promoter, triggers ATF4-dependent gene expression regulate CAR cells under conditions scarcity microenvironment. vitro murine xenograft models demonstrate potential system effectively restrict site. This targeted not only enhances safety minimizing activity but also fitness reducing exhaustion. By validating pathophysiologically regulatable tumors, our findings address key limitations current pave way innovative strategies targeting malignancies.

Язык: Английский

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Comprehensive transcriptome profiling in sepsis induced by pyogenic liver abscess

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, Год журнала: 2025, Номер unknown, С. 167905 - 167905

Опубликована: Май 1, 2025

Sepsis is a critical condition characterized by dysregulated immune response to infection, leading widespread inflammation, tissue damage, organ failure, and often death. It cause of morbidity mortality, particularly in intensive care units, due its complex pathophysiology involving dysregulation, coagulation abnormalities, metabolic disturbances. Pyogenic liver abscess (PLA) significant cause, especially developing countries where incidence rising. PLA, an infectious disease, can lead sepsis, termed sepsis secondary PLA (SLA). This study aimed identify key genes non-coding RNAs involved the pathogenesis treatment SLA. We performed RNA sequencing on peripheral blood samples from healthy individuals, SLA patients, patients after seven days therapy. Integrated bioinformatics analysis identified 4549 differentially expressed (DE) mRNAs, 9808 DE lncRNAs, 467 circRNAs, 292 miRNAs between controls. Additionally, 3199 6018 161 132 were before mRNAs both comparisons associated with responses; lncRNAs linked B cell receptor signaling pathway osteoclast differentiation; circRNAs connected Chagas disease pathway; implicated MAPK estrogen pathways. constructed lncRNA/circRNA-miRNA-mRNA networks explore regulatory relationships, validating 16 ceRNAs through RT-PCR. These findings provide new insights into treatment, potentially guiding development novel therapies.

Язык: Английский

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Navigating the metabolic landscape of regulatory T cells: from autoimmune diseases to tumor microenvironments

Current Opinion in Immunology, Год журнала: 2024, Номер 92, С. 102511 - 102511

Опубликована: Дек. 13, 2024

Язык: Английский

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Transcription network of SLC7A11 (xCT) in colon cancer provides clinical targets for metabolic regulation and cell proliferation

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Июнь 3, 2024

Abstract Colorectal cancer (CRC) represents the third leading cause of cancer-related deaths. Knowledge covering diverse cellular and molecular data from individual patients has become valuable for diagnosis, prognosis, treatment selection. Here, we present in-depth comparative RNA-seq analysis 32 CRC pairing tumor healthy tissues (total 73 samples). Strict thresholds differential expression genes (DEG) revealed an interconnection between nutrients, metabolic program, cell cycle pathways. Among upregulated DEGs, focused on Xc- system, composed proteins SLC7A11 (xCT) SLC3A2 genes, along with several interacting genes. To assess oncogenic potency system in a setting, applied knowledge-based approach, analyzing gene perturbations CRISPR screens. The study set 27 co-dependent that were strongly correlated fitness across many types. Alterations these 13 large-scale studies (e.g., by mutations copy number variation) found to enhance overall survival progression-free patients. In agreement, overexpression cells drives progression allowing effective management redox level, induction stress response mechanisms, most notably, enhanced activity ion/amino acid transporters, enzymes acting de novo nucleotide synthesis. We also highlight positive correlation patient responsiveness different chemotherapy treatments, immune infiltration ( e.g., myeloid-derived suppressor cells) tumors as measure their immunosuppressive activity. This illustrates interpretation synthesizing multiple layers leads functional mechanistic insights into role its associated tumorigenesis therapeutics.

Язык: Английский

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Bulk RNA analysis identified the characteristics and immunoinvasive patterns of osimertinib resistance in patients with non-small cell lung cancer

Research Square (Research Square), Год журнала: 2024, Номер unknown

Опубликована: Сен. 11, 2024

Non-small cell lung cancer (NSCLC) remains a leading cause of cancer-related mortality worldwide, with epidermal growth factor receptor (EGFR) mutations being common driver. Osimertinib, third-generation EGFR tyrosine kinase inhibitor (TKI), has shown efficacy in treating NSCLC patients harboring mutations. However, resistance to osimertinib poses significant clinical challenge. This study aims identify key genes associated and elucidate their underlying mechanisms inform new therapeutic strategies. Utilizing comprehensive bioinformatics approach, we conducted differential expression analysis, enrichment consensus clustering, drug sensitivity protein-protein interaction (PPI) network construction, immune infiltration analysis. Our findings revealed 126 genes, including KRT14, KRT16, KRT17, KRT5, KRT6A, KRT6B, TP63, TRIM29, that are potentially pivotal resistance. Enrichment analyses indicated involvement biological processes such as epidermis development keratinocyte differentiation, pathways like valine, leucine, isoleucine degradation. Immune analysis showed downregulation 14 types the resistant group, notable negative correlations between hub specific cells. We constructed diagnostic model an area under curve (AUC) greater than 0.9,,validated externally, demonstrating robust performance. Interaction networks, mRNA-TF, RBP-mRNA, lncRNA-miRNA-mRNA, provided insights into complex regulatory

Язык: Английский

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Applying metabolic control strategies to engineered T cell cancer therapies

Metabolic Engineering, Год журнала: 2024, Номер 86, С. 250 - 261

Опубликована: Окт. 25, 2024

Язык: Английский

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