P-108 An interplay between immune cells and microbiota drives the spontaneous regression of colorectal polyps in familial adenomatous polyposis pig model

Familial Adenomatous Polyposis (FAP) is the most common adenomatous polyposis syndrome, in which patients develop hundreds to thousands of polyps at an early age. The high number significantly increases risk their progression colorectal cancer (CRC). To investigate development and mechanism FAP, we used APC1311 mutant pigs our recent research has revealed that a significant proportion these undergo spontaneous regression instead developing cancer. Although polyp human have been reported, however explaining this process lacking. Using porcine model, study was able reveal pathological immunological characteristics regressing polyps. Furthermore, role immune cells microbiota tumor microenvironment on found. regular colonoscopy time course morphological changes were examined. By immunohistochemical staining, distinct between progressing analysed. A set molecular methods including single-cell RNA 16S rRNA sequencing gene expression microbiome polyps, irregular crypt distortion, notable stromal expansion, increased accumulation apoptotic identified. contained lower levels mucus or polysaccharides (0.6% vs. 8.5%), fewer Ki67+ crypts (23.1% 56.2%), but notably higher numbers CD3+ stroma (27.62% 17.25%) comparing increase MPO+ (11.1% 3.5%) IBA1+ (9.4% 4.1%) infiltrating observed. At level, found decreased Ki67, LGR5 MUC2 genes involved pathway, such as caspase 3, granzyme B perforin, sequencing, distinguished profile epithelial regressive from clusters progressive Regressing enriched neutrophils CD8+ T cells, while Tregs C1Q+ macrophages. showed Helicobacter Fusobacterium Our complex interplay contributes APC pigs. This provides promising findings for prevention treatment CRC.