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Updated: Jul 11, 2026

Advances in Human Induced Pluripotent Stem Cell-Derived Chimeric Antigen Receptor-Expressing Natural Killer Cells
Published on: February 14, 2025
Intercellular transfer of carcinoembryonic antigen from tumor cells to NK cells
Noam Stern-Ginossar1, Shlomo Nedvetzki, Gal Markel
1Lautenberg Center for General and Tumor Immunology, Hadassah Medical School, Hebrew University, Jerusalem, Israel.
Abstract:
The inhibition of NK cell killing is mainly mediated via the interaction of NK inhibitory receptors with MHC class I proteins. In addition, we have previously demonstrated that NK cells are inhibited in a class I MHC-independent manner via homophilic carcinoembryonic Ag (CEA) cell adhesion molecules (CEACAM1)-CEACAM1 and heterophilic CEACAM1-CEA interactions. However, the cross-talk between immune effector cells and their target cells is not limited to cell interactions per se, but also involves a specific exchange of proteins. The reasons for these molecular exchanges and the functional outcome of this phenomenon are still mostly unknown. In this study, we show that NK cells rapidly and specifically acquire CEA molecules from target cells. We evaluated the role of cytotoxicity in the acquisition of CEA and demonstrated it to be mostly killing independent. We further demonstrate that CEA transfer requires a specific interaction with an unknown putative NK cell receptor and that carbohydrates are probably involved in CEA recognition and acquisition by NK cells. Functionally, the killing of bulk NK cultures was inhibited by CEA-expressing cells, suggesting that this putative receptor is an inhibitory receptor.
Insights
Natural killer (NK) cells acquire carcinoembryonic antigen (CEA) from target cells, independent of killing. This transfer suggests a novel inhibitory mechanism involving CEA recognition by NK cells.
Area of Science:
- Immunology
- Cell Biology
- Molecular Interactions
Background:
- Natural killer (NK) cell inhibition is primarily mediated by NK inhibitory receptors interacting with MHC class I proteins.
- NK cell inhibition can also occur independently of MHC class I, through interactions involving carcinoembryonic antigen (CEA) and its receptor CEACAM1.
- Cellular cross-talk involves protein exchange, but the mechanisms and functional consequences remain largely unexplored.
Purpose of the Study:
- To investigate the acquisition of CEA molecules by NK cells from target cells.
- To determine the role of cytotoxicity in CEA acquisition by NK cells.
- To elucidate the mechanism and functional implications of CEA transfer between cells.
Main Methods:
- Evaluation of CEA acquisition by NK cells from target cells.
- Assessment of the role of cytotoxicity in the CEA acquisition process.
- Investigation of the molecular interactions and carbohydrate involvement in CEA recognition and transfer.
Main Results:
- NK cells rapidly and specifically acquire CEA molecules from target cells.
- CEA acquisition is largely independent of NK cell-mediated cytotoxicity.
- CEA transfer necessitates interaction with a specific, yet unidentified, NK cell receptor, likely involving carbohydrate recognition.
Conclusions:
- NK cells actively acquire CEA from target cells through a killing-independent mechanism.
- The process involves a specific NK cell receptor, suggesting a novel pathway for cellular communication.
- The observed inhibition of NK cell killing by CEA-expressing cells indicates this putative receptor functions as an inhibitory receptor.
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