Globally,
colorectal cancer (CC) is the third leading cause of mortality associated with
cancer. Natural killer (NK) cells are a major class of cells that are responsible for eliminating
tumor cells and
cytokine production. NK cell-mediated production of
interferon gamma (IFN-γ) has
antiviral, immunoregulatory and anti-
tumor properties.
IL-15 is important in linking
inflammation with
cancer. For instance,
IL-15 promotes humoral and cell-mediated immune responses to inhibit
tumor growth.
IL-15 inhibits
colitis-associated colon
carcinogenesis by inducing antitumor immunity. However, the effect of NK cell-mediated IFN-γ on
IL-15 expression in CC progression remains unknown.
mRNA and
protein level were detected using reverse transcription-quantitative PCR and western blotting, respectively. IFN-γ concentrations were detected using ELISAs. The cytotoxicity of NK-92 cells on SW480 cells was detected using cytoTox 96® non-radioactive cytotoxicity assays. Cell apoptosis and cell proliferation was detected using flow cytometry and
CCK-8 assays, respectively.
IL-2 was used for NK-92 stimulation,
IL-15 antibodies were used to neutralize
IL-15 bioactivity. For the present study, 21 patients with CC and 21 healthy volunteers were enrolled at the First Affiliated Hospital of Xi'an Jiaotong University.
IL-15 mRNA and
protein expression were significantly lower in NK cells isolated from the CC group compared with healthy volunteer group.
IL-2 enhanced the production/secretion of IFN-γ in addition to enhancing NK-92 cell-mediated killing of SW480 cells. Compared with the control group, NK-92 cells treated with
IL-2 alone significantly increased cell apoptosis, BAX expression levels as well as phosphorylated (p)-
Janus kinase 2 and p-STAT1
protein levels, whilst reducing cell viability and Bcl-2
protein levels in SW480 cells. These observations were not made when treated with
IL-2 and polyclonal antibody (pAb) targeting
IL-15. Taken together, NK cell-mediated IFN-γ served a pivotal role in CC by regulating
IL-15. The effects of
IL-2 induced IFN-γ were abolished by pAb
IL-15 treatment. The mechanisms of action behind how IFN-γ regulates
IL-2 is unclear, and is a promising area for future research.