Role of metabolic transformation in cancer immunotherapy resistance: molecular mechanisms and therapeutic implications

Discover Oncology, Journal Year: 2025, Volume and Issue: 16(1)

Published: April 2, 2025

Immunotherapy in the treatment of cancer, with immune inhibitors helps many cancer types. Many patients still encounter resistance to these treatments, though. This is mediated by metabolic changes tumour microenvironment and cells. The development novel treatments overcome boost immunotherapy's effectiveness depends on changes. review concentrates molecular mechanisms through which transformation contributes immunotherapy resistance. Additionally, research therapeutic approaches that target pathways enhance for We used databases available PubMed, Scopus, Web Science perform a thorough peer-reviewed literature. focusing tumor microenvironment, mechanisms, metabolism. study covers oxidative phosphorylation, glycolysis, lipid metabolism, amino acid An immunosuppressive produced cells, such as dysregulated enhanced glutaminolysis, increased glycolysis (Warburg effect). Myeloid-derived suppressor cells regulatory T are promoted, responses suppressed, cell activity impaired when lactate other metabolites build up. metabolism acids arginine tryptophan, nutrients crucial function. By enhancing their function alterations aid checkpoint inhibitors. Metabolic change plays key role Gaining knowledge processes can help develop efficient improve effectiveness. In order determine best targets intervention, future studies should concentrate patient-specific profiling.

Language: Английский

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Identifying Aberrant 1CM-Related Pathways by Multi-Omics Analysis and Validating Tumor Inhibitory Effect of One-Carbon Donor Betaine in Gastric Cancer

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(8), P. 3841 - 3841

Published: April 18, 2025

Metabolic reprogramming, a well-established hallmark of gastric carcinogenesis, has been implicated in driving tumor progression. Nevertheless, the precise mechanisms through which these metabolic alterations orchestrate cancer (GC) pathogenesis remain incompletely elucidated. We conducted metabolomic analyses plasma samples obtained from 334 patients with GC and healthy individuals to identify differential metabolites pathways. Transcriptome sequencing was on six pairs tissues, joint analysis transcriptome metabolome performed. Single-cell data were acquired co-analyzed metabolomics investigate abnormalities at single-cell level. Finally, four representative selected using Random Forest subjected cellular experiments elucidate exert their effects. Metabolomic revealed that serine glycine metabolism, glycolysis, glutamate metabolism significantly altered GC, suggesting one-carbon (1CM)-related pathways are aberrantly activated. A combined transcriptome, indicated related oxidative phosphorylation, nucleotide amino acid epithelial cells GC. Cellular demonstrated donor metabolite betaine could inhibit activity, invasion, migration while activating phosphorylation AMPKα. In conclusion, 1CM-related pathway play significant roles influences warrant further investigation.

Language: Английский

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Optimizing CD8+ T cell-based immunotherapy via metabolic interventions: a comprehensive review of intrinsic and extrinsic modulators

Experimental Hematology and Oncology, Journal Year: 2024, Volume and Issue: 13(1)

Published: Oct. 22, 2024

Abstract CD8 + T cells are integral to the effective management of cancer and infectious diseases due their cytotoxic functions. The efficacy these is profoundly influenced by metabolic state, which regulates activation, differentiation, longevity. Accordingly, modulation pathways within crucial for enhancing effectiveness cell-based immunotherapy. Precise control paramount in optimizing therapeutic outcomes minimizing potential toxicities associated with treatment. Importantly, exogenous metabolites augment cell responses critically evaluated, especially through vivo evidence that underscores promise. This review also addresses current challenges, including need precise avoid adverse effects, development targeted delivery systems ensure efficient metabolite cells, inherent variability states among patients may influence treatment outcomes. Addressing hurdles will be successful integration interventions into established immunotherapeutic regimens.

Language: Английский

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From multi-omics to predictive biomarker: AI in tumor microenvironment

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 15

Published: Dec. 23, 2024

In recent years, tumors have emerged as a major global health threat. An increasing number of studies indicate that the production, development, metastasis, and elimination tumor cells are closely related to microenvironment (TME). Advances in artificial intelligence (AI) algorithms, particularly large language models, rapidly propelled research medical field. This review focuses on current state strategies applying AI algorithms metabolism explores expression differences between normal cells. The analysis is conducted from perspectives metabolomics interactions within TME, further examining roles various cytokines. describes potential approaches through which can facilitate metabolic studies, offers valuable perspective for deeper understanding pathological mechanisms tumors.

Language: Английский

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A review of carbohydrate polymer-synthesized nanoparticles in cancer immunotherapy: Past, present and future perspectives

International Journal of Biological Macromolecules, Journal Year: 2024, Volume and Issue: 286, P. 138195 - 138195

Published: Dec. 5, 2024

Language: Английский

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