Though landmark histological studies correlated T cell infiltration with effector memory CD45RO+CD8+ T cells with survival in CRC (3, 4), the success of T cell targeting immunotherapy in CRC has been limited to a rare subset with high microsatellite instability (microsatellite instability–high [MSI-H] tumors that only represent ~15% of CRC) that are characterized by a higher degree of mutation due to defective DNA mismatch repair (5–9). The gene discussed is CD8A; the disease is colorectal carcinoma.