Exercise-associated epigenetic remodeling and TCR repertoire dynamicsin Lynch Syndrome carriers (RRBS)

Recent data suggest exercise as a non-pharmacologic preventive strategy, yet the epigenetic and immunological mechanisms underlying its protective effects in this population remain unclear. Here, we perform integrative multi-omics profiling of DNA methylation, gene expression, and the T cell receptor (TCR) repertoire in LS carriers participating in a 52-week aerobic cycling intervention.

We identify compartment-specific DNA methylation changes, including innate immune activation in cfDNA and oncogenic pathway repression in tissue. Transcriptomic integration highlights ISL1 as a key exercise-repressed gene and FLCN as a CRC-associated methylation target. TCR analysis reveals increased systemic repertoire diversity and tissue-specific clonal convergence, thus suggesting antigen-driven recruitment.