Related Experiment Video
Updated: Aug 19, 2025
Analysis of Human Natural Killer Cell Metabolism
Published on: June 22, 2020
The tumor microenvironment drives NK cell metabolic dysfunction leading to impaired antitumor activity
Nicola Tumino1, Carina B Nava Lauson2, Silvia Tiberti2
1Immunology Research Area, Innate Lymphoid Cells Unit, Bambino Gesù Children's Hospital IRCCS, Rome, Italy.
Abstract:
NK cells represent key players capable of driving antitumor immune responses. However, the potent immunosuppressive activity of the tumor microenvironment (TME) may impair their effector function. Here, we strengthen the importance of metabolic interactions between NK cells and TME and propose metabolic dysfunction as one of the major mechanisms behind NK failure in cancer treatment. In particular, we described that TME has a direct negative impact on NK cell function by disrupting their mitochondrial integrity and function in pediatric and adult patients with primary and metastatic cancer. Our results will help to design new strategies aimed at increasing the NK cell antitumor efficacy by their metabolic reprogramming. In this regard, we reveal an unprecedented role of IL15 in the metabolic reprogramming of NK cells enhancing their antitumor functions. IL15 prevents the inhibitory effect of soluble factors present in TME and restores both the metabolic characteristics and the effector function of NK cells inhibited by exposure to malignant pleural fluid. Thus, we propose here that IL15 may be exploited as a new strategy to metabolically reprogram NK cells with the aim of increasing the efficacy of NK-based immunotherapy in a wide range of currently refractory adult and pediatric solid tumors.
Insights
The tumor microenvironment (TME) impairs natural killer (NK) cell function through metabolic disruption. Interleukin-15 (IL15) can overcome this, enhancing NK cell antitumor activity for cancer immunotherapy.
Area of Science:
- Immunology
- Cancer Biology
- Metabolic Research
Background:
- Natural killer (NK) cells are crucial for anti-tumor immunity.
- The tumor microenvironment (TME) often suppresses NK cell function.
- Metabolic dysfunction is a key factor in NK cell failure during cancer treatment.
Purpose of the Study:
- To investigate the impact of TME on NK cell metabolism and function.
- To identify mechanisms by which TME impairs NK cells.
- To explore strategies for enhancing NK cell antitumor efficacy through metabolic reprogramming.
Main Methods:
- Analysis of NK cell mitochondrial integrity and function in cancer patients.
- Assessment of metabolic reprogramming strategies for NK cells.
- Evaluation of the role of Interleukin-15 (IL15) in restoring NK cell function.
Main Results:
- The TME negatively impacts NK cell mitochondrial integrity and function in both pediatric and adult cancer patients.
- Metabolic dysfunction contributes significantly to NK cell failure in cancer.
- IL15 effectively counteracts the immunosuppressive effects of the TME.
- IL15 restores metabolic characteristics and effector functions of NK cells exposed to malignant pleural fluid.
Conclusions:
- Metabolic reprogramming of NK cells is a promising strategy to enhance cancer immunotherapy.
- IL15 plays a critical role in the metabolic reprogramming of NK cells, boosting their anti-tumor functions.
- IL15 can be utilized to overcome TME-induced NK cell suppression, offering a novel therapeutic approach for various solid tumors.
More Related Videos
06:55Measurement of Natural Killer Cell-Mediated Cytotoxicity and Migration in the Context of Hepatic Tumor Cells
Published on: February 22, 2020
08:19Transfer of Manipulated Tumor-associated Neutrophils into Tumor-Bearing Mice to Study their Angiogenic Potential In Vivo
Published on: July 20, 2019
Related Concept Videos
02:17The Tumor Microenvironment
01:27Cytotoxic T Cells-mediated Immune Response
Immunological surveillance is the ability of immune cells to monitor and eliminate infected cells with intracellular pathogens, neoplastically transformed cells, and cells with non-self antigens. Cytotoxic T cells and NK...
01:27Tumor Immunotherapy
01:28Cells of the Innate Immune Response
Phagocytes
Phagocytes police the peripheral tissues by removing cellular debris and responding to the invasion of foreign substances or pathogens. Many phagocytes attack and remove microorganisms even before lymphocytes detect them. The human body has two general...
01:28Chemotherapy-Induced Nausea and Vomiting: Neurokinin-1 Receptor Antagonists
02:53Adaptive Mechanisms in Cancer Cells
Some of the advantages that cancer cells have on normal cells include - enhanced ability to divide without terminally differentiating, induce new blood vessel formation,...