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Metabolic programming and immune suppression in the tumor microenvironment
Emily N Arner1, Jeffrey C Rathmell2
1Department of Medicine, Vanderbilt University Medical Center (VUMC), Nashville, TN, USA.
Cancer Cell
|February 21, 2023
Summary
Tumor cells and their microenvironment exhibit metabolic heterogeneity, influencing cancer progression and immune evasion. Targeting this metabolic plasticity offers new strategies to enhance immunotherapies.
Area of Science:
- Oncology
- Cancer Metabolism
- Immunology
Background:
- Increased glucose metabolism is a hallmark of cancer, aiding diagnosis and monitoring.
- The tumor microenvironment (TME) comprises diverse cells that interact with cancer cells, influencing tumor growth and immune evasion.
- Cellular and metabolic heterogeneity within tumors arise from TME composition, cell states, location, and nutrient availability.
Purpose of the Study:
- To discuss how metabolic programming within the TME drives tumor proliferation, progression, and metastasis.
- To explore the potential of targeting metabolic heterogeneity to overcome immune suppression and improve immunotherapies.
Main Methods:
- Review and synthesis of current literature on cancer metabolism and the tumor microenvironment.
- Discussion of metabolic reprogramming in cancer cells and immune cells within the TME.
- Analysis of the role of metabolic heterogeneity in tumor progression and immune evasion.
Main Results:
- Metabolic reprogramming in cancer cells and TME components fuels tumor growth, metastasis, and immune evasion.
- Altered nutrient availability and signaling in the TME induce metabolic suppression of effector immune cells and promote regulatory immune cells.
- Metabolic heterogeneity contributes to therapeutic resistance and immune evasion.
Conclusions:
- Metabolic programming of cells within the TME is crucial for tumor proliferation, progression, and metastasis.
- Targeting metabolic heterogeneity presents a promising therapeutic strategy to enhance immunotherapies by overcoming immune suppression.
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