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

Objectives: 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).

Methods: 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.

Results: SPC25 was overexpressed in LUAD (p < 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 (p < 0.0001). Mechanistically, TFDP1 was a transcriptional activator of SPC25. Knocking down TFDP1 hindered GLN metabolism (p < 0.05) and potentiated NK cell killing ability against LUAD cells, while overexpression of SPC25 reversed the effects of TFDP1 knockdown.

Conclusion: This study intended to verify the inhibitory effect of TFDP1 on NK cell anti-tumor immunity by activating SPC25-mediated LUAD glutamine metabolism.