Intercellular transfer of carcinoembryonic antigen from tumor cells to NK cells

Noam Stern-Ginossar, Shlomo Nedvetzki, Gal Markel, Roi Gazit, Gili Betser-Cohen, Hagit Achdout, Memet Aker, Richard S. Blumberg, Daniel M. Davis, Ben Appelmelk, Ofer Mandelboim

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)4424-4434
Number of pages11
JournalJournal of Immunology
Volume179
Issue number7
DOIs
StatePublished - 1 Oct 2007
Externally publishedYes

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