POLE-mutated and MSI tumors have an active TME not only for the high number of TILs, but also for the huge amount of tumor specific neo-antigens, generated by genetic alteration acquired due to impaired DNA replication fidelity (POLE) and defective DNA MMR system (MSI-H) [4, 14] (Figure 3). The gene discussed is POLE; the disease is neoplasm.