Resistance to RT and PD-L1 blockade have been explored in a murine model of HNSCC, in which that the immune checkpoint receptor, T cell immunoglobulin mucin-3 (TIM-3), a negative regulator of Th1 immunity, was found to be expressed by a fraction of TIL CD3+CD8+ T cells and TIL CD4+CD25+Foxp3+Tregs in cancers treated with RT and anti-PD-L1 inhibitors. The gene discussed is CD274; the disease is head and neck squamous cell carcinoma.