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Metabolites in the tumor microenvironment: Key drivers of immune cell fate and function as therapeutic targets in
Xiao-Ping Zhao1, Chu-Tian Mai2, Yi-Lin Zhao1
1Dr. Neher's Biophysics Laboratory for Innovative Drug Discovery, State Key Laboratory of Mechanism and Quality of Chinese Medicine, School of Pharmacy, Macau University of Science and Technology, Macau SAR, China.
Abstract:
Tumor cells employ multiple strategies to evade immune detection, largely facilitated by the immunosuppressive tumor microenvironment (iTME). This environment not only hinders therapeutic efficacy but also drives metabolic reprogramming of tumor cells, resulting in localized nutrient deprivation and the accumulation of immunomodulatory metabolites. Metabolites such as lactic acid and adenosine accumulate under hypoxic and poorly perfused conditions, directly altering immune cell function and promoting tumor immune escape. Consequently, these metabolites have emerged as promising therapeutic targets in cancer immunotherapy. In this review, we systematically examine how TME-derived metabolites influence diverse immune cell populations and summarize current clinical progress in targeting their production and signaling pathways for anticancer treatment.
Insights
Tumor cells use the tumor microenvironment (TME) to hide from the immune system. Metabolites in the TME, like lactic acid and adenosine, are key targets for new cancer immunotherapies.
Area of Science:
- Immunology
- Metabolism
- Oncology
Background:
- Tumor cells evade immune detection via the immunosuppressive tumor microenvironment (iTME).
- The iTME causes metabolic reprogramming, leading to nutrient deprivation and accumulation of immunomodulatory metabolites.
- Metabolites like lactic acid and adenosine promote tumor immune escape by altering immune cell function.
Purpose of the Study:
- To review how tumor microenvironment (TME)-derived metabolites impact immune cells.
- To summarize clinical progress in targeting these metabolites for cancer immunotherapy.
Main Methods:
- Systematic literature review.
- Analysis of metabolite production and signaling pathways.
- Examination of immune cell modulation by metabolites.
Main Results:
- TME metabolites significantly influence diverse immune cell populations.
- Accumulation of lactic acid and adenosine under hypoxia alters immune responses.
- Metabolites are critical mediators of tumor immune escape.
Conclusions:
- Targeting TME-derived metabolites represents a promising strategy in cancer immunotherapy.
- Further research into metabolite-driven immunosuppression can optimize therapeutic approaches.
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