Pembrolizumab in metastatic gastric cancer with Mismatch-Repair Deficiency: comprehensive molecular analysis to the clinical response

Tumors with DNA mismatch repair (dMMR) deficiency are often accompanied by high microsatellite instability (MSI-H). Due to the large accumulation of somatic mutations, MSI-H tumors often present excessive number of neoantigens as well as infiltrating lymphocytes and exhibit high expression level of programmed death ligand 1 (PD-L1) on their membrane. Such characteristics of MSI-H tumors render them susceptible to immunotherapeutic approach such as immune checkpoint inhibitors. MSI-H tumors account for 2 - 4% of all diagnosed cancer, primiarly observed in colorectal and endometrial carcinomas. In gastric cancer (GC), MSI-H tumors constitute 9 - 22% and the incidence of metastatic MSI-H GC in Korea ranges from 4 - 7%.