B7 同源物 6 通过 NKp30 下游 ERK 通路促进 NK 细胞对宫颈癌的杀伤活性

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.

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 ® Non-Radioactive Cytotoxicity Assay. Western blotting was used to detect the extracellular signal-regulated kinase (ERK) phosphorylation level in NK cells.

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.

B7-H6 may enhance the killing capacity of NK cells by activating the NKp30 downstream ERK signaling pathway.