An early animal study revealed that anti-CTLA-4 antibodies could act synergistically with PD-1 blockade to increase effector T cell infiltration and allow continuous expansion of tumor-specific T cells, thereby shifting TIM from suppressive to inflammatory.67 Currently, there is one FDA-approved combination – nivolumab (3 mg/kg) plus low-dose ipilimumab (1 mg/kg) for treating metastatic melanoma, renal cell carcinoma (RCC; Supplementary Table 2), and dMMR/MSI-H CRC (Table 2). Here, PDCD1 is linked to metastatic melanoma.