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

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. This study aims to elucidate the interaction between fibrotic CRCs and CAFs by comparing the phenotypic characteristics of bulk tumor tissues and their corresponding CAFs. Overall design: RNA-seq profiling of fresh samples of surgically resected human colorectal carcinoma