NK cells play a key role in innate immunity, having potent cytolytic activity against virally infected and tumor cells. NK-cell activity is regulated by inhibitory and activatory receptors expressed at the cell surface and their interaction with associated ligands. CD160 binds to MHC class Ia and Ib with low affinity and triggers cytotoxic function in peripheral blood NK cells, as well as cytokine production, including IFN-γ, TNF-α, and IL-6.11,12 Only a limited number of human activating NK-cell receptors have been demonstrated to induce cytokine production and release in addition to cytotoxicity. The PI3K signaling molecule is required for CD160-mediated cytokine release, with involvement of the signaling molecules Syk and ERK upstream and downstream of PI3K, respectively. Recent work has demonstrated CD160 expression in malignant human B cells. CD160 expressed on the surface of B-cell chronic lymphocytic leukemia (CLL) mimicked CD160 functions in normal NK and T cells: cellular activation, up-regulation of BCL-2 and BCL-XL, and improved in vitro cell survival and cytokine production, specifically IL-6 and IL-8. PI3K/Akt signaling was required for CD160-mediated functions in CLL cells. Similar "aberrant" expression of a signaling molecule, CD3-receptor-associated protein tyrosine kinase or ζ-associated protein-70 (ZAP-70), was reported in CLL. Like CD160, ZAP-70 was initially described exclusively in T cells and NK cells,18 but was subsequently detected in mature and immature human B-lymphoid malignancies,19?–21 as well as normal murine and human B cells.
Farren T W, Giustiniani J, Liu F T, et al. Differential and tumor-specific expression of CD160 in B-cell malignancies[J]. Blood, 2011, 118(8): 2174-2183.