Together with the epigenetic data of Nair et al. showing promoter demethylation and reduced H3K9me3 at the TIGIT locus in CRC tissue [30], our findings support a model in which MSI-driven genomic instability and deregulated epigenetic landscape act in concert with a highly inflamed TME to promote upregulation of TIGIT and other immune checkpoint molecules in MSI CRC. Here, TIGIT is linked to colorectal carcinoma.