Role of Meox1 in promoting lung tumor vascularization and impairing CD8(+) T cell mediated immunity.

INTRODUCTION: Endothelial cells play a critical role in tumor-associated vasculature formation and immune modulation, and dysregulation of transcription factors (TFs) such as Meox1 has been associated with various cancers, including non-small cell lung cancer (NSCLC). Meox1 has been implicated in promoting both tumor-promoting and immune-suppressing functions. METHODS: In this study, to systematically map TF dynamics across cancer and immune cells, we performed scRNA-seq on tumor tissues and used the SCENIC framework for regulon analysis, revealing cell-type-specific gene regulatory networks. We investigated the functional role of Meox1 in NSCLC by employing a siRNA-based knockdown approach to selectively reduce its expression. RESULTS: Our preliminary findings reveal that siRNA-mediated Meox1 knockdown significantly impairs the capacity of tube formation at the cellular level. Furthermore, we observed a marked reduction in tumor cell proliferation and an increase in CD8 expression, a marker of T-cell activity in an animal model system, indicating that Meox1 may also play a regulatory role in immune-mediated tumor suppression. DISCUSSION: Our findings not only deepen our understanding of the molecular mechanisms underlying lung cancer progression but also open new avenues for the development of targeted therapies aimed at restoring tumor-associated endothelial cell function and enhancing immune responses against cancer.