Ferdinandos Skoulidis

Ferdinandos Skoulidis, MD, PhD is an Associate Professor in the Department of Thoracic/Head and Neck Medical Oncology at MD Anderson Cancer Center. He is globally recognized for defining STK11/LKB1 co-mutations as the dominant molecular determinant of primary immunotherapy resistance in KRAS-mutant non-small cell lung cancer (NSCLC). His landmark genomic analyses of large NSCLC clinical cohorts demonstrated that STK11/LKB1 loss-of-function mutations, which occur in approximately 20% of KRAS-mutant lung adenocarcinomas, are associated with a profoundly immunosuppressive tumor microenvironment characterized by low TIL infiltration, high neutrophil content, CXCL5/IL-8 upregulation, and near-complete absence of PD-L1 expression. He showed that STK11/LKB1 mutations predict poor response to PD-1/PD-L1 checkpoint inhibitors even in PD-L1-positive or TMB-high tumors, challenging the utility of these biomarkers in KRAS/STK11 co-mutant patients. Dr. Skoulidis also characterized the metabolic reprogramming induced by LKB1 loss that contributes to immune suppression, including upregulation of arginase activity and neutrophil-derived immunosuppression, and is leading therapeutic strategies to overcome STK11/LKB1-driven resistance.