posted on 2023-04-03, 19:41authored byTakayasu Ideta, Boyang Li, Christopher Flynn, Yuichi Igarashi, Geoffrey Lowman, Tim Looney, Thomas J. Devers, John Birk, Faripour Forouhar, Charles Giardina, Daniel W. Rosenberg
Supplemental Figure S2. Heatmap of differentially expressed genes. (A) Heatmap of 88 differentially expressed genes in normal (left) and ACF (right) epithelial samples. (B) Heatmap of 82 differentially expressed genes in normal (left) and ACF (right) stromal samples
Funding
State of Connecticut Department of Public Health
NIH
NCI
American Institute of Cancer Research
California Walnut Commission
History
ARTICLE ABSTRACT
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.
Decreased CD8 T-cell infiltration within proximal colon ACF occurs within the context of a robust inflammatory response and potential stromal cell senescence, thus providing new insight into potential promotional drivers for tumors in the proximal colon.