Fibroblast-Derived Thrombospondin 2 Shapes the Immune-Exclusionary Environment at Invasive Fronts in Colorectal Cancer [scRNA-seq]

Fibrotic colorectal cancers (CRC) are characterized by immune exclusion driven by activated stroma, particularly by cancer-associated fibroblasts (CAFs). We identified that the matricellular protein thrombospondin-2 (THBS2) is highly expressed in the stroma of fibrotic CRCs. We performed orthotopic implantation of CMS4-like mouse tumor organoid (MTO) into WT and Thbs2 KO mice. Tumors developed in Thbs2 KO mice were considerably smaller and exhibited increased CD8 T cell infiltration and higher numbers of apoptotic tumor cells compared with WT mice. Our aim is to elucidate how Thbs2 in tumor microenvironment influences tumor growth. Overall design: Tumors derived from orthotopic implanted mouse tumor organoids (MTOs) harboring mutations in Apc, Trp53, Kras, and Tgfbr2 in the rectum of wild-type, Thbs1KO and Thbs2KO mice were processed into single-cell suspension and analyzed using scRNA-seq