AUTHOR=Huang Zhenyao , Chen Xia , Wang Yun , Yuan Jiali , Li Jing , Hang Wenlu , Meng Hao TITLE=SLC7A11 inhibits ferroptosis and downregulates PD-L1 levels in lung adenocarcinoma JOURNAL=Frontiers in Immunology VOLUME=15 YEAR=2024 URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2024.1372215 DOI=10.3389/fimmu.2024.1372215 ISSN=1664-3224 ABSTRACT=Introduction

Lung adenocarcinoma (LUAD) is a prevalent form of lung cancer originating from lung glandular cells with low survival rates despite recent therapeutic advances due to its diverse and complex nature. Recent evidence suggests a link between ferroptosis and the effectiveness of anti-PD-L1 therapy, with potential synergistic effects.

Methods

Our study comprehensively analyzed the expression patterns of ferroptosis regulators in LUAD and their association with prognosis and PD-L1 expression. Furthermore, we identified two distinct subtypes of LUAD through consensus clustering of ferroptosis regulators, revealing significant tumor heterogeneity, divergent PD-L1 expression, and varying prognoses between the subtypes.

Results

Among the selected ferroptosis regulators, SLC7A11 emerged as an independent prognostic marker for LUAD patients and exhibited a negative correlation with PD-L1 expression. Subsequent investigations revealed high expression of SLC7A11 in the LUAD population. In vitro experiments demonstrated that overexpression of SLC7A11 led to reduced PD-L1 expression and inhibited ferroptosis in A549 cells, underscoring the significant role of SLC7A11 in LUAD. Additionally, pan-cancer analyses indicated an association between SLC7A11 and the expression of immune checkpoint genes across multiple cancer types with poor prognoses.

Discussion

From a clinical standpoint, these findings offer a foundation for identifying and optimizing potential combination strategies to enhance the therapeutic effectiveness of immune checkpoint inhibitors and improve the prognosis of patients with LUAD.