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Tumor Microenvironment-Induced Immunometabolic Reprogramming of Natural Killer Cells
Andrea M Chambers1, Kyle B Lupo1, Sandro Matosevic1,2
1Department of Industrial and Physical Pharmacy, Purdue University, West Lafayette, IN, United States.
Frontiers in Immunology
|November 24, 2018
Summary
Tumor metabolism hinders natural killer cell effectiveness. Targeting adenosine signaling can improve immunotherapies for solid tumors.
Area of Science:
- Immunology
- Cancer Biology
- Metabolic Research
Background:
- Tumor growth, metastasis, and immune cell function are regulated by energy metabolism.
- Natural killer (NK) cells are crucial for tumor eradication but their function is impaired in the tumor microenvironment.
- Hypoxia and associated adenosinergic signaling create an immunosuppressive tumor microenvironment.
Purpose of the Study:
- To investigate how tumor metabolism affects NK cell function.
- To explore the role of hypoxia and adenosine in NK cell-mediated anti-tumor activity.
- To identify immunometabolic targets for enhancing NK cell-based immunotherapies.
Main Methods:
- Analysis of tumor metabolism and its impact on immune cells.
- Investigation of hypoxia-induced changes in the tumor microenvironment.
- Characterization of adenosinergic signaling pathways involving CD39 and CD73.
Main Results:
- Altered tumor metabolism compromises NK cell persistence and anti-tumor functions.
- Hypoxia promotes adenosine generation, leading to NK cell immunosuppression.
- Adenosine signaling acts as an immunometabolic checkpoint, reducing NK cell effectiveness.
Conclusions:
- Tumor-associated metabolic reprogramming and hypoxia-driven adenosine production suppress NK cell anti-tumor activity.
- Targeting adenosinergic signaling represents a promising strategy for overcoming NK cell exhaustion.
- Engineering NK cells with enhanced metabolic fitness is crucial for effective adoptive immunotherapies against solid tumors.
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