CD8A and cancer: Both the genomics and the TME of MSI-positive tumors contribute to the remarkable response rates: (i) MSI-positive tumors generate a great amount of neo-epitopes [129,130,131,134], which tend to be subclonal since MMRd-induced mutations are predominantly subclonal and derive in highly heterogeneous tumors [135]; (ii) MSI-positive cancers are highly infiltrated with CD8+ T cells [136]; and (iii) MSI-positive cancers express high levels of multiple immune checkpoint molecules, including PD1 and PD-L1 [137].