In 2020, 90% of new trials utilizing PD-1/PD-L1 inhibitors have been in combination studies.13 In our model of murine colon carcinoma, we demonstrate that the inhibitory receptors PD-1 and TIGIT are upregulated in the tumor infiltrating Tregs, CD4+ and CD8+ T cells and their respective cognate ligands, PD-L1 and CD155, are expressed in the TME (Figure 1). The gene discussed is PVR; the disease is colon carcinoma.