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MSI-High Colorectal CA : Treatment

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MSI-H colorectal cancers show a prominent lymphoid infiltrate consisting of cytotoxic (CD8+) T-lymphocytes. However, despite this the 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.

These discoveries have led to the development of several therapeutic monoclonal antibodies inhibiting PD-1 or PD-L1 (immune checkpoint inhibitors). US Food & Drug Administration has recently approved anti-PD-1 drug pembrolizumab for the treatment of metastatic/refractory MSI-H colorectal carcinomas.

This image of MSI-High colorectal carcinoma shows poorly-formed glands infiltrated by lymphocytes and neutrophils. Small foci (<20% of tumor) of conventional adenocarcinoma or mucinous carcinoma may be seen in MSI-High colorectal carcinomas.

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