MSI-High Colorectal CA : Immunology
One of the prominent features of MSI-high colorectal carcinomas is the presence of numerous tumor-infiltrating lymphocytes. The edge of the tumor often shows lymphoid aggregates or follicles with or without germinal centers. The lymphocytes infiltrating tumor microenvironment are cytotoxic (CD8+) T-lymphocytes and activated Th1 cells secreting interferon-ã. This results from the presence of numerous neoantigens (mutated proteins) caused by the hyper-mutated state of the tumor cells. Despite the active immune response, MSI-H tumor cells are not destroyed by the immune system due to upregulation of various immune inhibitory molecules (checkpoints) by the tumor cells. These checkpoints include PD-1 (Programmed Death 1) and its ligands PD-L1 and PD-L2; CTLA-4 (cytotoxic T-lymphocyte-associated protein 4); LAG-3 (lymphocyte-activation gene 3); and IDO (indoleamine (2,3) dioxygenase.