In immunologically cold melanoma models, low-dose whole-brain radiation therapy (LD-WBRT) 4 Gy single fraction reduced intracranial tumors and improved survival rates, while a high-dose radiation-based in situ vaccination (ISV) in 12 Gy single fraction immune-cytokines and anti-CTLA-4 effectively eradicated primary flank tumors. Here, CTLA4 is linked to melanoma.