CD40LG Downregulation in Lung Adenocarcinoma: A Prognostic Biomarker Linked to Immune Cell Infiltration and Survival Outcomes

<b>Background:</b> Lung adenocarcinoma (LUAD) continues to pose a major challenge in cancer treatment, characterized by low survival rates, particularly in metastatic instances. Although immunotherapy has become a common approach for treating LUAD, its success rate is merely 20%, hindered by the absence of effective biomarkers. This limitation is likely influenced by the tumor's immune microenvironment. CD40LG, an important immune molecule, has emerged as a crucial factor in modulating the tumor immune environment and affecting the outcomes of immunotherapy. Nevertheless, its exact mechanisms in LUAD remain unclear, requiring more research. <b>Methods:</b> Through a correlation analysis of prognosis and clinical traits across multiple cancers, we determined that CD40LG is significant in LUAD. This role was confirmed using various public datasets. We evaluated CD40LG protein expression in 94 LUAD and nearby non-cancerous tissues via immunohistochemistry. To gauge immune cell infiltration, we employed multiplex immunofluorescence staining on tissue microarrays. Additionally, <i>in vitro</i> assays were carried out to explore the effects of CD40LG modulation on the behavior of LUAD cells. <b>Results:</b> Various cancers, including LUAD, exhibited down-regulation of CD40LG, which correlated with a worse prognosis. In LUAD tissues, higher CD40LG expression was associated with longer Progression-Free Survival (PFS) and Overall Survival (OS). Moreover, CD40LG expression negatively correlated with the TNM stage and T stage in LUAD. Elevated CD40LG levels were linked to increased infiltration of CD8+ T cells. <i>In vitro</i> studies showed that modulating CD40LG affected LUAD cell metastasis and proliferation. <b>Conclusion:</b> Our study demonstrates the pivotal role of CD40LG in LUAD, proposing its potential utility as a biomarker for prognosis and immunotherapy. The correlation between CD40LG expression, immune cell infiltration, and clinical outcomes emphasizes its importance in tumor-immune dynamics and the efficacy of immunotherapy.