Tumor-induced apoptosis of human IL-2-activated NK cells: Role of natural cytotoxicity receptors

Alessandro Poggi, Anna Maria Massaro, Simone Negrini, Paola Contini, Maria Raffaella Zocchi

Research output: Contribution to journalArticlepeer-review


We provide evidence that tumor cells can induce apoptosis of NK cells by engaging the natural cytotoxicity receptors (NCR) NKp30, NKp44, and NKp46. Indeed, the binding between NCR on NK cells and their putative ligands on tumor target cells led to NK cell apoptosis, and this event was abolished by blocking NCR/NCR-ligand interaction by anti-NCR-specific mAbs. The engagement of NCR induced up-regulation of Fas ligand (FasL) mRNA, FasL protein synthesis, and release. In turn, FasL interacting with Fas at NK cell surface causes NK cell suicide, as apoptosis of NK cells was inhibited by blocking FasL/Fas interaction with specific mAbs. Interestingly, NK cell apoptosis, but not killing of tumor target cells, is inhibited by cyclosporin A, suggesting that apoptosis and cytolysis are regulated by different biochemical pathways. These findings indicate that NCR are not only triggering molecules essential for antitumor activity, but also surface receptors involved in NK cell suicide.

Original languageEnglish
Pages (from-to)2653-2660
Number of pages8
JournalJournal of Immunology
Issue number5
Publication statusPublished - Mar 1 2005

ASJC Scopus subject areas

  • Immunology


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