More critically, resistance to targeted therapies (e.g., VEGF inhibitors) and immune checkpoint blockers (e.g., anti-PD-1/PD-L1 agents) has become increasingly prominent — 40% of patients with clear cell renal cell carcinoma (ccRCC) fail to respond to combination therapies, a phenomenon fundamentally linked to the high heterogeneity of the Tumor Microenvironment (TME) (4). Here, VEGFA is linked to neoplasm.