High-dose radiation therapy (HDRT, >10–20 Gy/fractions) converts immunologically “cold” tumors into “hot” by determining the death of cancer cells, resulting in the release of proinflammatory mediators, such as damage-associated molecular patterns (DAMPs), high-mobility group box 1 protein (HMGB1), ATP, and calreticulin, which stimulate Toll-like receptor 4 (TLR4). The gene discussed is TLR4; the disease is cancer.