Resistance mechanisms include both tumor-intrinsic factors, such as loss of antigen presentation, abberations in interferon signaling, and upregulation of alternate checkpoints (LAG-3, TIM-3, TIGIT); and tumor-extrinsic factors, such as infiltration by regulatory T cells (Tregs), myeloid-derived suppressor cells (MDSCs), and a broadly immunosuppressive tumor microenvironment (TME) (9–12). The gene discussed is TIGIT; the disease is neoplasm.