PCNA: a novel cancer-associated ligand for the NK cell receptor NKp44 (162.10)

Michael Brusilovsky, Benyamin Rosental, Uzi Hadad, Kerry Campbell, Angel Porgador

Research output: Contribution to journalMeeting Abstractpeer-review

Abstract

Natural Cytotoxicity Receptors (NCRs: NKp30, NKp44, and NKp46) trigger NK cell-mediated lysis of tumors and virus-infected cells. Previous studies identified BAT3, B7-H6 and Vimentin as cellular ligands for NKp30 and NKp46, respectively. However, our knowledge of NCR-mediated recognition of cancer cells remains incomplete. NKp44 is expressed exclusively in primates and its expression is induced upon activation of NK cells. We have discovered that NKp44 directly recognizes Proliferating Cell Nuclear Antigen (PCNA), which is recruited within target cells to the NK immunological synapse. Over-expression of PCNA was found to inhibit NK cell cytotoxicity in an NKp44-dependent manner. Also, the cytoplasmic immunoreceptor tyrosine-based inhibitory motif (ITIM) in NKp44 is crucial for PCNA-meditated NK cell inhibition. Since PCNA over-expression can promote cancer survival, our study reveals a novel immune evasion mechanism. Our results also further emphasize the role of nuclear proteins as ligands for Natural Cytotoxicity Receptors.
Original languageEnglish GB
JournalThe Journal of Immunology
Volume188
Issue number1
StatePublished - 2012

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