The B7 family member B7-H6 is a tumor cell ligand for the activating natural killer cell receptor NKp30 in humans

Abstract

Cancer development is often associated with the lack of specific and efficient recognition of tumor cells by the immune system. Natural killer (NK) cells are lymphocytes of the innate immune system that participate in the elimination of tumors. We report the identification of a tumor cell surface molecule that binds NKp30, a human receptor which triggers antitumor NK cell cytotoxicity and cytokine secretion. This previously unannotated gene belongs to the B7 family and, hence, was designated B7-H6. B7-H6 triggers NKp30-mediated activation of human NK cells. B7-H6 was not detected in normal human tissues but was expressed on human tumor cells, emphasizing that the expression of stress-induced self-molecules associated with cell transformation serves as a mode of cell recognition in innate immunity.

Nidogen-1 is a novel extracellular ligand for the NKp44 activating receptor

“…23 On the other hand, molecularly unrelated cellular ligands have been shown to bind NKp30 (B7H6 and BAT3/BAG6) and NKp44 (21spe-MLL5). 24-26 …”

“…29,30 NKp30 triggers cytotoxicity and cytokine release upon binding B7H6 or BAT3 at the cell surface. 24,25,31 Besides NCRs, other activating receptors, including NKG2D and DNAM-1, contribute to trigger the NK cell-mediated cytotoxicity. 32-34 Ligands specific for these receptors have been extensively characterized: MICA/B and ULBPs molecules are recognized by NKG2D, while PVR and Nectin-2 (belonging to the Nectin family), are ligands for DNAM-1.…”

NCR+ILC3 concentrate in human lung cancer and associate with intratumoral lymphoid structures

“…Although NCRs were found to bind some viral glycoproteins, their ligands on tumour cells have only partially been defined 10,11 . B7-H6 and, very recently, a novel isoform of the mixed-lineage leukemia (MLL5) protein have been shown to be expressed on a large panel of tumour cells 12,13 and are recognized by NKp30 and NKp44 receptors, respectively. Although a role of NK cells in anti-tumour immunity has been established, such a role for other ILC populations remains largely unexplored.…”

B7-H6 : un nouveau signal d’alarme pour les cellulesnatural killer

“…Dans ce cadre nous venons de caracté-riser un ligand tumoral de NKp30 [9]. Cette protéine de 51 kDa référencée sous le nom DKFZp686O24166 a pour proches homologues B7-H1 et B7-H3, deux membres de la famille B7.…”