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Updated: Nov 28, 2025
Analysis of Human Natural Killer Cell Metabolism
Published on: June 22, 2020
Modulating NK cell metabolism for cancer immunotherapy
Iñigo Terrén1, Ane Orrantia1, Joana Vitallé1
1Biocruces Bizkaia Health Research Institute, Immunopathology Group, Barakaldo, Spain.
Abstract:
Natural killer (NK) cells are lymphocytes with potent antitumor functions and, therefore, multiple NK cell-based cancer immunotherapies have been developed and are currently being tested. However, there is a necessity to find new means to improve these therapies, and immunometabolism represents an attractive target. NK cell effector functions are intricately linked to their metabolism, and modulating the latter could be the key to release their full potential. In this review, we have summarized how NK cell metabolism is regulated during some processes, such as maturation, viral infection, and cytokine stimulation. Additionally, we provide an overview of how NK cell metabolism is affected by current therapeutic approaches aimed to promote NK cell expansion and/or to increase their effector functions. We have also recapitulated several strategies that could help alleviating the metabolic impairment that characterizes tumor-infiltrating NK cells, and thus increase or restore their effector functions. Furthermore, we have reviewed several therapeutic approaches targeting cancer metabolism that could synergize with NK cell-based cancer immunotherapies, and thus enhance their efficacy.
Insights
Natural killer (NK) cells show promise in cancer immunotherapy. Understanding and targeting NK cell metabolism can enhance their anti-tumor functions and improve treatment efficacy.
Area of Science:
- Immunology
- Cancer Biology
- Metabolism
Background:
- Natural killer (NK) cells are crucial lymphocytes with significant anti-tumor capabilities, leading to the development of NK cell-based cancer immunotherapies.
- Current immunotherapies necessitate novel strategies to enhance NK cell efficacy, with immunometabolism emerging as a promising therapeutic target.
- NK cell effector functions are closely tied to their metabolic state, suggesting that metabolic modulation could unlock their full therapeutic potential.
Purpose of the Study:
- To review the regulation of NK cell metabolism during key biological processes like maturation, viral infection, and cytokine stimulation.
- To examine the impact of current therapeutic strategies on NK cell metabolism, expansion, and effector functions.
- To explore strategies for overcoming metabolic deficits in tumor-infiltrating NK cells and to identify metabolic therapies that synergize with NK cell-based immunotherapies.
Main Methods:
- Literature review of studies on NK cell metabolism, cancer immunotherapy, and metabolic targeting.
- Synthesis of information on NK cell metabolic regulation in various physiological and pathological contexts.
- Analysis of current and potential therapeutic interventions affecting NK cell function and metabolism.
Main Results:
- NK cell metabolism is dynamically regulated by maturation, infections, and cytokine signaling.
- Therapeutic interventions can influence NK cell metabolism, impacting their expansion and effector functions.
- Tumor microenvironments often impose metabolic constraints on NK cells, impairing their anti-tumor activity.
- Metabolic strategies targeting cancer and NK cells hold potential for synergistic therapeutic effects.
Conclusions:
- Modulating NK cell metabolism is a viable strategy to enhance their anti-tumor functions in cancer immunotherapy.
- Addressing metabolic impairments in tumor-infiltrating NK cells is critical for restoring their efficacy.
- Combined approaches targeting both NK cell metabolism and cancer metabolism may significantly improve immunotherapy outcomes.
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