NEDD4L suppresses PD-L1 expression and enhances anti-tumor immune response in A549 cells

Abstract

Background: Non-small cell lung cancer (NSCLC) poses a salient threat to public health. E3 ubiquitin ligase commonly functions as an anti-tumor role.

Objective: This study probed the effect of E3 ligase NEDD4L on A549 cells.

Methods: NEDD4L expression in NSCLC and its correlation with NSCLC patient's prognosis were predicted and verified. PD-L1 protein level was measured, and the correlation between NEDD4L and PD-L1 was analyzed. The effects of NEDD4L overexpression on the binding of NEDD4L to PD-L1 and ubiquitination level of PD-L1 were examined. Xenograft tumor model was established in mice. The volume and weight of xenograft tumors were recorded. The proportion of CD8⁺ T cells and contents of IL-2 and INF-γ were detected.

Results: NEDD4L expression was downregulated in NSCLC tissues and A549 cells, and correlated with poor prognosis of NSCLC patients. PD-L1 was upregulated in NSCLC and negatively correlated with NEDD4L. Overexpression of NEDD4L upregulated ubiquitination level of PD-L1 and reduced protein level of PD-L1. Overexpression of NEDD4L decreased tumor volume and weight and enhanced proportion of CD8⁺ T cells and contents of IL-2 and INF-γ.

Conclusions: Collectively, overexpression of NEDD4L suppressed PD-L1 protein level through ubiquitination, thereby enhancing anti-tumor immune response and retarding NSCLC progression.

Keywords: A549 cells; NEDD4L; Non-small cell lung cancer; PD-L1; Tumor immunity; Ubiquitination.