The Epithelial-Stromal Microenvironment in Early Colonic Neoplasia.
Mol Cancer Res
; 20(1): 56-61, 2022 01.
Article
em En
| MEDLINE
| ID: mdl-34670862
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. IMPLICATIONS 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.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Células Estromais
/
Neoplasias do Colo
/
Células Epiteliais
Idioma:
En
Ano de publicação:
2022
Tipo de documento:
Article