A team from Guangzhou University of Chinese Medicine elucidates how immunometabolism and oxidative stress mechanisms intersect to promote cancer progression and age-related decline, and proposes traditional Chinese medicine formulations as modulators of redox homeostasis and immune metabolic pathways for novel therapeutic approaches.
Key points
Interplay of ROS and immunometabolism: Mitochondrial dysfunction and NADPH oxidases generate ROS that disrupt immune cell metabolic adaptation via NF-κB and Nrf2 signaling, accelerating inflammation in both cancer and aging.
TCM interventions: Bioactive compounds from Astragali Radix, Lycii Fructus, baicalin and saikosaponin target oxidative stress-immunometabolic axes, modulate SIRT1, PI3K/Akt, and enhance antioxidant enzymes (SOD, CAT) to delay senescence and inhibit tumor growth.
Common mechanisms: Chronic inflammation, metabolic checkpoints via IDO1/Arg1 and PD-L1 upregulation, and ferroptosis pathways link immunosenescence and tumor immune evasion, suggesting senolytics and NOX inhibitors as dual-purpose therapies.
Why it matters:
Elucidating the immunometabolism–oxidative stress axis reveals dual-action targets for TCM compounds, offering new integrated therapies against aging and cancer.
Q&A
What is immunometabolism?
How does oxidative stress impact aging and cancer?
What role do TCM compounds play?
What is ferroptosis and its relevance?
Read full article
Academy
Immunometabolism in Aging and Cancer
Immunometabolism refers to how immune cells generate and use energy to perform their functions. Just as muscles need fuel for movement, immune cells rely on metabolic pathways such as glycolysis (breaking down glucose), oxidative phosphorylation (generating ATP in mitochondria), amino acid metabolism, and fatty acid oxidation to grow, divide, and produce signaling molecules.
In healthy youth, immune cells maintain balance by switching between pathways:
- Resting immune cells use low-level oxidative phosphorylation to meet basic energy needs.
- Activated immune cells shift to glycolysis even when oxygen is present (known as the Warburg effect) to rapidly generate building blocks for growth and defense.
During aging, key changes occur:
- Metabolic decline: Reduced mitochondrial function lowers energy output, causing immune cells to weaken.
- Chronic inflammation: Senescent cells secrete inflammatory factors (SASP), and immune cells become locked in a pro-inflammatory state, termed "inflammaging."
- Immunosenescence: Dysfunctional metabolism leads to fewer naive T cells and impaired responses to infections or cancer cells.
In the tumor microenvironment, cancer cells hijack nutrients and oxygen:
- Glucose competition: Tumors consume large amounts of glucose, starving immune cells of fuel for glycolysis.
- Lactate buildup: Excess lactate acidifies tissues, suppressing T cell and natural killer (NK) cell activity.
- Fatty acid and cholesterol overload: Alters macrophage polarization toward a pro-tumor (M2) state and drives T cell exhaustion.
Understanding immunometabolism reveals targets for longevity interventions:
- Antioxidants (e.g., glutathione, thioredoxin) restore redox balance and protect mitochondria from damage.
- Senolytics clear senescent cells, reducing SASP and healthy metabolic restoration.
- Metabolic modulators (e.g., mTOR inhibitors, AMPK activators) reprogram immune cell energy use to improve function.
- Traditional Chinese Medicine formulations offer multi-target compounds that enhance antioxidant defenses, modulate key pathways like Nrf2 and NF-κB, and support immune cell metabolism.
By restoring healthy metabolic flexibility in immune cells, researchers aim to delay age-related decline, improve vaccine responses, and strengthen anti-tumor immunity. Immunometabolism bridges basic energy processes to practical strategies in longevity science and oncology, making it a vital area for future therapies.
