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Updated: Mar 15, 2026
Measurement of Natural Killer Cell-Mediated Cytotoxicity and Migration in the Context of Hepatic Tumor Cells
Published on: February 22, 2020
[HMGB1 as metabolic weapon in the arsenal of natural killer cells]
G Gdynia1,2
1Pathologisches Institut, Universität Heidelberg, Im Neuenheimer Feld 224, 69120, Heidelberg, Deutschland. georg.gdynia@med.uni-heidelberg.de.
Abstract:
The German Nobel Prize winner Otto Warburg discovered the importance of glycolysis in cancer cells in the 1920s. Nearly one century later the inhibition of tumor glycolysis in cancer cells could literally be the Achilles Heel in cancer therapy. Surprisingly, we could show that Natural Killer (NK) cells pursue this strategy. They employ specific metabolic weapons to eliminate cancer cells by targeting tumor glycolysis. In colon cancer cells a specifically modified form of high mobility group box 1 (HMGB1) protein released by NK cells induced a previously unknown form of cell death. This new link between the killing of cancer cells and the innate immune system opened up new perspectives for immunotherapy in oncology.
Insights
Natural Killer (NK) cells target tumor glycolysis, a key cancer vulnerability discovered by Otto Warburg. NK cells use modified HMGB1 protein to induce a novel cell death pathway in colon cancer, offering new immunotherapy perspectives.
Area of Science:
- Oncology
- Immunology
- Metabolic pathways
Background:
- Otto Warburg identified glycolysis's importance in cancer cells in the 1920s.
- Targeting tumor glycolysis is a promising cancer therapy strategy.
- Natural Killer (NK) cells are part of the innate immune system.
Purpose of the Study:
- To investigate if NK cells target tumor glycolysis.
- To identify the mechanisms NK cells use to eliminate cancer cells.
- To explore new immunotherapy strategies for cancer.
Main Methods:
- Analysis of NK cell interactions with colon cancer cells.
- Investigation of metabolic pathways targeted by NK cells.
- Identification of specific proteins released by NK cells and their effects on cancer cells.
Main Results:
- NK cells were shown to target and inhibit glycolysis in cancer cells.
- A modified high mobility group box 1 (HMGB1) protein released by NK cells induced a novel form of cell death in colon cancer cells.
- A new link was established between innate immunity and cancer cell killing via metabolic targeting.
Conclusions:
- NK cells employ metabolic strategies to eliminate cancer cells by targeting tumor glycolysis.
- Modified HMGB1 protein released by NK cells triggers a unique cancer cell death pathway.
- This discovery opens new avenues for developing immunotherapies that target cancer metabolism.
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