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Introduction Lynch syndrome (LS) confers a high lifetime risk of colorectal cancer (CRC) due to germline mismatch repair deficiency (dMMR) and somatic second-hit loss. While dMMR crypt foci have been identified in histologically normal LS colon, progression to cancer is uncommon, suggesting effective immune surveillance. A better understanding of the adaptive immune response in LS may help explain cancer risk variation and inform future approaches to surveillance and prevention.This study aimed to characterise the spatial T-cell receptor (TCR) repertoire across tumour and non-tumour bowel in LS-associated CRC, assessing whether patterns of T-cell expansion and diversity are consistent with immune-mediated selection throughout the Lynch bowel.Methods Six surgical resection specimens (five colorectal, one small bowel) from individuals with LS-associated cancer were analysed using systematic spatial sampling across each specimen. Histologically distinct regions were identified on H&E staining to guide sampling of cancer and normal mucosa. One specimen was fresh-frozen and five were PAXgene-fixed. Five cases included paired cancer and normal tissue, and one included normal tissue alone.In total, 105 spatially resolved regions were analysed using FUME-TCRseq, a sensitive RNA-based method for TCR sequencing. TCR repertoire features, including abundance and diversity, were analysed using the Immunarch R package and examined in relation to clinicopathological variables.Results Clonal T-cell expansion was consistently observed in tumour regions ( figure 1), with shared T-cell clonotypes detected between cancer and adjacent normal bowel, suggesting common antigen-driven immune responses. Clonotype density (clonotypes/mm2) did not differ significantly by germline pathogenic variant (MLH1 vs MSH2), TNM stage (early vs late), tumour location, or tissue type.However, TCR diversity was significantly higher in right-sided colonic tumours (p = 6.10 × 10-7) and in the small bowel tumour (p = 0.0096) compared with left-sided tumours. Overall, cancer tissue showed lower TCR diversity than normal mucosa (p = 1.46 × 10-5), consistent with clonal dominance within the tumour microenvironment.Conclusions This multi-region analysis demonstrates that adaptive immunity plays a key role in shaping LS-associated CRC, with evidence of clonal T-cell expansion and immune selection across the Lynch bowel. The presence of shared T-cell clonotypes in tumour and non-tumour tissue supports ongoing immune surveillance beyond established cancer. These findings are clinically relevant, suggesting that variation in immune response may contribute to differences in cancer risk and progression in LS, and may inform future strategies for personalised surveillance, risk stratification, and immune-based prevention or interception.Abstract O20 Figure 1T cell clones expand around the diseased Lynch syndrome bowel