TFDP1 activates SPC25-mediated glutamine metabolism to repress anti-tumor immunity of NK cells in lung adenocarcinoma

The main purpose of this study is to investigate the specific role of SPC25 in the anti-tumor immune process of Natural killer (NK) cells in lung adenocarcinoma (LUAD). The differentially expressed gene SPC25 was screened by the Cancer Genome Atlas database. The effect of SPC25 on the anti-tumor immunity of NK cells was evaluated by immunofluorescence, flow cytometry, lactate dehydrogenase kit, and enzyme-linked immunosorbent assay. The influence of SPC25 on glutamine (GLN) metabolism was examined by the GLN metabolism-related kit and Western blot. The interaction between SPC25 and TFDP1 was assessed by luciferase reporter gene detection and ChIP. SPC25 was overexpressed in LUAD (<i>p</i> &lt; 0.0001), being capable of reducing levels of cytotoxicity and cytokines in NK cells. SPC25 repressed the function of NK cells by activating GLN metabolism (<i>p</i> &lt; 0.0001). Mechanistically, TFDP1 was a transcriptional activator of SPC25. Knocking down TFDP1 hindered GLN metabolism (<i>p</i> &lt; 0.05) and potentiated NK cell killing ability against LUAD cells, while overexpression of SPC25 reversed the effects of TFDP1 knockdown. This study intended to verify the inhibitory effect of TFDP1 on NK cell anti-tumor immunity by activating SPC25-mediated LUAD glutamine metabolism.