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Published on: March 17, 2023
Role of metabolic transformation in cancer immunotherapy resistance: molecular mechanisms and therapeutic
Sandesh Shende1, Jaishriram Rathored2, Tanushree Budhbaware1
1Central Research Laboratory and Molecular Diagnostics, School of Allied Health Sciences, Datta Meghe Institute of Higher Education and Research, Sawangi (Meghe), Wardha, 442001, Maharashtra, India.
Background:
Immunotherapy in the treatment of cancer, with immune inhibitors helps in many cancer types. Many patients still encounter resistance to these treatments, though. This resistance is mediated by metabolic changes in the tumour microenvironment and cancer cells. The development of novel treatments to overcome resistance and boost immunotherapy's effectiveness depends on these metabolic changes.
Objective:
This review concentrates on the molecular mechanisms through which metabolic transformation contributes to cancer immunotherapy resistance. Additionally, research therapeutic approaches that target metabolic pathways to enhance immunotherapy for resistance.
Methods:
We used databases available on PubMed, Scopus, and Web of Science to perform a thorough review of peer-reviewed literature. focusing on the tumor microenvironment, immunotherapy resistance mechanisms, and cancer metabolism. The study of metabolic pathways covers oxidative phosphorylation, glycolysis, lipid metabolism, and amino acid metabolism.
Results:
An immunosuppressive tumour microenvironment is produced by metabolic changes in cancer cells, such as dysregulated lipid metabolism, enhanced glutaminolysis, and increased glycolysis (Warburg effect). Myeloid-derived suppressor cells and regulatory T cells are promoted, immune responses are suppressed, and T cell activity is impaired when lactate and other metabolites build up. changes in the metabolism of amino acids in the pathways for arginine and tryptophan, which are nutrients crucial for immune function. By enhancing their function in the tumour microenvironment, these metabolic alterations aid in resistance to immune checkpoint inhibitors.
Conclusion:
Metabolic change plays a key role in cancer immunotherapy resistance. Gaining knowledge of metabolic processes can help develop efficient treatments that improve immunotherapy's effectiveness. In order to determine the best targets for therapeutic intervention, future studies should concentrate on patient-specific metabolic profiling.
Insights
Cancer cells
Area of Science:
- Oncology
- Cancer Immunology
- Metabolic Pathways
Background:
- Immunotherapy, including immune inhibitors, shows promise in various cancers.
- Treatment resistance remains a significant challenge, often driven by metabolic alterations in the tumor microenvironment.
- Understanding these metabolic changes is crucial for developing novel therapeutic strategies.
Purpose of the Study:
- To review the molecular mechanisms linking metabolic reprogramming to cancer immunotherapy resistance.
- To explore therapeutic approaches targeting metabolic pathways to overcome resistance and enhance immunotherapy efficacy.
Main Methods:
- Comprehensive literature review of PubMed, Scopus, and Web of Science databases.
- Focus on tumor microenvironment, immunotherapy resistance, and cancer metabolism.
- Analysis of key metabolic pathways including glycolysis, lipid, amino acid metabolism, and oxidative phosphorylation.
Main Results:
- Metabolic reprogramming creates an immunosuppressive tumor microenvironment (e.g., Warburg effect, dysregulated lipid metabolism, glutaminolysis).
- Accumulation of metabolites like lactate suppresses immune responses and impairs T cell function.
- Alterations in arginine and tryptophan metabolism disrupt immune cell function, contributing to resistance against immune checkpoint inhibitors.
Conclusions:
- Metabolic reprogramming is a critical factor in cancer immunotherapy resistance.
- Targeting metabolic pathways offers a promising strategy to improve immunotherapy effectiveness.
- Future research should prioritize patient-specific metabolic profiling for precise therapeutic interventions.
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