Cell Systems, Journal Year: 2024, Volume and Issue: 15(12), P. 1225 - 1244
Published: Dec. 1, 2024
Language: Английский
Cellular and Molecular Immunology, Journal Year: 2025, Volume and Issue: unknown
Published: March 4, 2025
Abstract Autologous T-cell therapies show limited efficacy in chronic lymphocytic leukemia (CLL), where acquired immune dysfunction prevails. In CLL, disturbed mitochondrial metabolism has been linked to defective activation and proliferation. Recent research suggests that lipid regulates function differentiation T cells, yet its role CLL remains unexplored. This comprehensive study compares patients healthy donors, revealing critical dependence on exogenous cholesterol for human expansion following TCR-mediated activation. Using multi-omics functional assays, we found cells present viably frozen samples of with (CLL cells) showed impaired adaptation deprivation inadequate upregulation key transcription factors. exhibited altered storage, increased triacylglycerols decreased cholesterol, inefficient fatty acid oxidation (FAO). Functional consequences reduced FAO were studied using from inherent disorders. Reduced was associated lower but did not affect implicates low levels as a primary factor limiting proliferation CLL. displayed fewer less clustered rafts, potentially explaining the synapse formation observed these patients. Our findings highlight significant disruptions drivers deficiencies underscoring pivotal modulating could enhance presenting novel immunotherapeutic approaches improve outcome this challenging disease.
Language: Английский
Citations
3
Immunity, Journal Year: 2024, Volume and Issue: 57(8), P. 1734 - 1751
Published: Aug. 1, 2024
Language: Английский
Citations
11
Cell Death Discovery, Journal Year: 2025, Volume and Issue: 11(1)
Published: April 9, 2025
Abstract The complex interplay between cancer progression and immune senescence is critically influenced by metabolic reprogramming in T cells. As cells age, especially within the tumor microenvironment, they undergo significant shifts that may hinder their proliferation functionality. This manuscript reviews how alterations contribute to cell discusses potential therapeutic strategies aimed at reversing these changes. We explore interventions such as mitochondrial enhancement, glycolytic inhibition, lipid metabolism adjustments could rejuvenate senescent cells, potentially restoring efficacy suppression. review also focuses on significance of with aging further explores future direction metabolism-based immunotherapy
Language: Английский
Citations
1
Cancer Cell, Journal Year: 2024, Volume and Issue: unknown
Published: Dec. 1, 2024
Language: Английский
Citations
7
Proceedings of the National Academy of Sciences, Journal Year: 2024, Volume and Issue: 121(52)
Published: Dec. 18, 2024
Inhibiting indoleamine 2,3 dioxygenase (IDO) for anticancer therapy has garnered significant attention in recent years. However, current IDO inhibitors face challenges which limit their clinical application. Here, we genetically engineered a high tryptophan-expressing Clostridium butyricum (L-Trp CB) strain that can colonize tumors strictly following systemic administration. We revealed butyrate produced by L-Trp CB inhibit activity, preventing tryptophan catabolism and kynurenine accumulation tumors. In addition, the large released provide discrete signals support CD8+ T cell activation energy metabolism within tumor microenvironment. observed significantly restored proportion function of cells, leading to delayed growth both mouse rabbit multiple models with limited side effects. here synthetic biology treatment strategy enhanced immunotherapy inhibiting activity reprogramming response
Language: Английский
Citations
6
bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown
Published: June 12, 2024
Abstract Nutrient stress represents a significant barrier for antitumor immunity, and tumor interstitial fluid (TIF) often contains metabolites that hinder immune function. However, it is difficult to isolate the effects of nutrient from other suppressive factors. Thus, we employed chemically-defined cell culture medium based on metabolomic profile TIF: Tumor Interstitial Fluid Medium (TIFM). Culture CD8 + T cells in TIFM limited expansion impaired effector functions upon restimulation, suggesting alone sufficient drive dysfunction. We identified phosphoethanolamine (pEtn), phospholipid intermediate, as driver pEtn dampened TCR signaling by depleting diacylglycerol required signal transduction. Reduction accumulation tumors improved intratumoral function control, plays dominant role TME immunosuppression.
Language: Английский
Citations
4
Cell Metabolism, Journal Year: 2024, Volume and Issue: unknown
Published: Nov. 1, 2024
Language: Английский
Citations
4
Journal for ImmunoTherapy of Cancer, Journal Year: 2024, Volume and Issue: 12(9), P. e009603 - e009603
Published: Sept. 1, 2024
Stage IV gastric cancer is a highly heterogeneous and lethal tumor with few therapeutic strategies. The combination of programmed cell death protein 1 inhibitors chemotherapy currently the standard frontline treatment regimen for advanced cancer. Nevertheless, it remains great challenge to screen beneficiaries immunochemotherapy expand indications this regimen.
Language: Английский
Citations
3
Gut, Journal Year: 2025, Volume and Issue: unknown, P. gutjnl - 333020
Published: Jan. 27, 2025
Background Fasting-mimicking diet (FMD) boosts the antitumour immune response in patients with colorectal cancer (CRC). The gut microbiota is a key host immunity regulator, affecting physiological homeostasis and disease pathogenesis. Objective We aimed to investigate how FMD protects against CRC via modulation. Design assessed probiotic species enrichment FMD-treated mice using faecal metagenomic sequencing. candidate were verified antibiotic-treated conventional germ-free mouse models. Immune landscape alterations evaluated single-cell RNA sequencing multicolour flow cytometry. microbiota-derived metabolites identified metabolomic profiling. Results Faecal profiling revealed Bifidobacterium pseudolongum mice. B. mediates effects by increasing tissue-resident memory CD8 + T-cell (TRM) population level of L-arginine, functional metabolite, increased mice; furthermore, L-arginine induced TRM phenotype vivo vitro. Mechanistically, transported solute carrier family 7-member 1 (SLC7A1) receptor T cells. Both improved anti-CTLA-4 efficacy orthotopic model. In CRC, cell number as accumulated. abundance cells was associated better prognosis CRC. Conclusion contributes producing L-arginine. This promotes differentiation into administration potential therapeutic strategy.
Language: Английский
Citations
0
Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 16
Published: Feb. 6, 2025
Circulating regulatory T cells (Tregs) are closely related to immune tolerance and maintenance of homeostasis. Perhaps, there is a unique cell phenotype for difficult-to-treat rheumatoid arthritis (D2T RA). Low-dose interleukin-2 (IL-2) has been considered the treatment autoimmune diseases. This study focused on uniqueness D2T RA lymphocyte subsets feasibility low-dose IL-2 therapy. Participants included 1,042 patients who were divided into three groups according presence or absence their response in last 6 months-new group, treated group-and 339 healthy controls (HCs). A total 381 patients-107, 151, 123 each experimental groups-received [0.5 million international units (MIU) per day, subcutaneous injection from day 1 5]. The absolute numbers peripheral blood detected by flow cytometry (FCM) serum cytokine levels bead array (CBA). number T, CD4+ Treg group was lower than that HC, new, groups. Compared with HC new ratio Th17/Treg increased. treated, had higher HC. negatively correlated disease activity index. could be increased therapy without any side effects. lymphocytes reduced, especially cells, resulting shift balance effector cells/Treg toward which ameliorated obvious
Language: Английский
Citations
0