cLynch a better understanding.

Almost half of colorectal cancers (CRC) arise in the setting of microsatellite instability (MSI) and underlying deficient mismatch repair (MMR) genes. About 10% of these MMR genetic deficiencies are germline, a pathology historically referred to as Lynch syndrome. It is widely recognized that MMR-deficient CRC have higher rates of tumor-infiltrating lymphocytes (TIL) and thus better responses to immunotherapy and overall better prognoses. But what about specifically Lynch-associated (i.e., germline MMR-deficient) CRC? A fascinating NCI study reveals, when looking only at patients with MMR-deficient CRC, Lynch-associated cancers had more neoantigen burdens in the exomes sequenced translating to consistently higher rates of TILs across several measurements which is probably all contributing to their significantly higher survival rates. TBL: Patients with Lynch-associated CRC have higher mutational loads with more neoantigens, stronger immune responses, and better survival.


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