B7 homolog 6 promotes the killing activity of natural killer cells against cervical cancer through the downstream ERK pathway of NKp30.

Background: Cervical cancer is a common female malignant tumor which lacks of effective immunotherapy drugs. There are a large number of studies about immune regulation of cervical cancer, but the involvement of innate immunity is rarely reported. As a ligand of NKp30, B7 homolog 6 (B7-H6) is involved in the immune regulation of various tumors. The aim of the present study was to clarify the effect of B7-H6 expression in HeLa cells on the killing function of natural killer (NK) cells. Methods: B7 H6 expression was changed in HeLa cells using short hairpin ribonucleic acid (RNA). The effect of B7-H6 on the killing function of NK cells was analyzed following cell co-culture. Flow cytometry was used to detect NKp30 expression, degranulation function, and perforin (PFP) and granzyme B (GZMB) secretion function of NK cells. Enzyme-linked immunosorbent assay was used to detect interferon-γ (INF-γ) production. The cytotoxicity of NK-92 cells was determined using the CytoTox 96 Results: Following the co-culture of NK-92 and HeLa cells with different B7-H6 expression levels, the NKp30 expression, NK-92 cell killing rate, PFP and INF-γ production, as well as degranulation function, were changed in NK cells; no effect on GZMB production was observed. Following cell co-culture, the ERK phosphorylation level in NK cells was gradually increased with the up-regulation of B7-H6. Conclusions: B7-H6 may enhance the killing capacity of NK cells by activating the NKp30 downstream ERK signaling pathway.