The Epithelial-Stromal Microenvironment in Early Colonic Neoplasia

Stromal cells play a central role in promoting the progression of colorectal cancer. Here, we analyze molecular changes within the epithelial and stromal compartments of dysplastic aberrant crypt foci (ACF) formed in the ascending colon, where rapidly developing interval cancers occur. We found strong activation of numerous neutrophil/monocyte chemokines, consistent with localized inflammation. The data also indicated a decrease in interferon signaling and cell-based immunity. The immune checkpoint and T-cell exhaustion gene PDCD1 was one of the most significantly upregulated genes, which was accompanied by a decrease in cytotoxic T-cell effector gene expression. In addition, CDKN2A expression was strongly upregulated in the stroma and downregulated in the epithelium, consistent with diverse changes in senescence-associated signaling on the two tissue compartments.

Automated summary

Stromal cells are crucial in promoting colorectal cancer progression, with involvement in localized inflammation, reduced interferon signaling and cell-based immunity. The upregulation of immune checkpoint and T-cell exhaustion gene PDCD1, accompanied by decreased expression of cytotoxic T-cell effector genes, is observed. CDKN2A expression is strongly upregulated in the stroma and downregulated in the epithelium, indicating diverse changes in senescence-associated signaling between these tissue compartments.