Abstract
BACKGROUND: Immunotherapy, particularly anti-PD-1 therapy, has assumed a progressively significant position in the management of non-small cell lung cancer (NSCLC), especially in lung adenocarcinoma (LUAD). Nevertheless, a subset of patients exhibit resistance to anti-PD-1 therapy, and the exploration of biomarkers for evaluating the responsiveness to anti-PD-1 therapy necessitates further investigation. FLT3LG is regarded as being associated with tumor diagnosis and immunotherapy in a variety of tumor types, but its function in LUAD is uncertain. METHODS: Bioinformatics analysis was conducted to evaluate the clinical value, functional enrichment, genetic correlation, and immune infiltration of FLT3LG in LUAD. We then used a mouse model to detect immune cell infiltration and relevant protein expression by flow cytometry and immunohistochemistry under anti-PD-1 treatment after overexpression of FLT3LG. The serum FLT3LG expression in LUAD patients was detected via ELISA, and PD-L1 expression in tumor samples was detected by immunohistochemistry. RESULTS: In LUAD patients, a better prognosis is associated with elevated FLT3LG expression. Among the genes strongly associated with FLT3LG, the majority were involved in immune-related processes and were enriched predominantly in immune-related pathways. Moreover, high expression of FLT3LG was significantly positively correlated with increased infiltration of multiple immune cells, including T cells and natural killer (NK) cells, in lung adenocarcinomas, as well as the expression of several immune cell markers, such as CD4 and CD8a. In a mouse model, overexpression of FLT3LG in mice subjected to subcutaneous graft tumor elicited a pronounced immune response and could enhance the efficacy of anti-PD-1 therapy. CONCLUSION: FLT3LG could be considered as a diagnostic and prognostic marker for LUAD and might play a role in enhancing the therapeutic response to immunotherapy in patients with LUAD.