It also shows that Foxo1 exerts its inhibitory effects by blocking transcription of the gene that encodes Tbx21, which is a known positive regulator of NK-cell development and function.
The research was reported in the journal Immunity.
“We discovered a pathway that cancer cells may use to block NK-cell function and evade immune responses,” says principal investigator Jianhua Yu, PhD, assistant professor of medicine and a member of the OSUCCC — James Leukemia Research Program.
“The findings may provide us an opportunity to enhance NK-cell antitumor activity,” he adds.
Yu and his colleagues used an animal model and human NK cells for the study. Key technical findings include:
- Foxo1 and Foxo3 control NK-cell maturation, but Foxo1 plays the major role;
- Reducing Foxo1 expression enhances NK-cell maturation;
- Foxo1 suppression of Tbx21 expression involves different mechanisms in human and mouse NK cells.