Single-cell spatial immune profiling for precision immunotherapy in Lynch syndrome

Abstract

Lynch syndrome (LS) is the most common hereditary colorectal cancer (CRC) predisposition syndrome, characterized by a high mutational burden and microsatellite instability-high (MSI-H) tumors. Immunology of LS-associated CRC (LS-CRC) is unique, with significant implications for treatment. Despite well-established knowledge of LS immunology, immunotherapy dose and treatment response can vary significantly based on local tumor immunity and specific germline pathogenic variant of LS genes. This variability necessitates tailored surveillance strategies and new personalised immunotherapy approaches for LS patients. LS-CRC often benefits from immunotherapy due to the distinct tumor microenvironment (TME) and the variety of tumor infiltrating lymphocytes (TILs). This perspective discusses a novel approach of analysing spatial TILs at a single-cell level using tumor whole slide images (WSIs) that accounts for the distinct TME of LS-CRC. By emphasizing the necessity of personalized medicine in hereditary cancer syndromes, the future research and clinical practices that enhance patient outcomes through precision oncology is inspired.