GAS6 potentiates tumor progression through modulating suppressive microenvironments

Although growth arrest-specific 6 (GAS6), the principal ligand of the TAM receptors (TYRO3, AXL, and MERTK), acts as a central coordinator of efferocytosis, no pan-cancer analysis has been conducted. We thus first analyzed GAS6 across thirty-three tumors based on the datasets on TCGA (The Cancer Genome Atlas), TCGA-XENA (UCSC Xena), and other publicly available repositories. We observed a correlation of aberrant expression of GAS6 with malignant transformation and cancer progression, which strongly predicts worse overall survival in multiple malignancies. Transcriptomic deconvolution revealed a clear positive correlation between GAS6 levels and macrophage infiltration and polarization. Our study systematically revealed the evidence establishing GAS6 as an oncogenic driver and a regulator of the immunosuppressive microenvironment across human cancers. These findings furnish a mechanistic rationale for therapeutically targeting the GAS6/TAM axis to subvert immune tolerance and potentiate chemoradiation.