The Epithelial-Stromal Microenvironment in Early Colonic Neoplasia.
The Epithelial-Stromal Microenvironment in Early Colonic Neoplasia.
复制标题
早期结肠肿瘤的上皮细胞微环境。
DOI：
10.1158/1541-7786.mcr-21-0202
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发表时间：
2022-01
期刊：
影响因子：
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通讯作者：
Rosenberg DW
中科院分区：
文献类型：
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作者：
Ideta T;Li B;Flynn C;Igarashi Y;Lowman G;Looney T;Devers TJ;Birk J;Forouhar F;Giardina C;Rosenberg DW
基质细胞在促进结直肠癌的进展中起着核心作用。在这里，我们分析分子内的上皮和间质室的发育不良异常隐窝灶（ACF）形成的升结肠，在快速发展的间隔癌发生。我们发现大量中性粒细胞/单核细胞趋化因子的强烈激活，与局部炎症一致。数据还表明干扰素信号传导和基于细胞的免疫力降低。免疫检查点和T细胞耗竭基因PDCD 1是最显著上调的基因之一，其伴随着细胞毒性T细胞效应基因表达的降低。此外，CDKN 2A表达在基质中强烈上调，在上皮中下调，这与两个组织区室上衰老相关信号的不同变化一致。近端结肠ACF内CD 8 T细胞浸润减少发生在强烈的炎症反应和潜在的基质细胞衰老的背景下，从而为近端结肠中肿瘤的潜在促进驱动因素提供了新的见解。
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 up-regulated genes, which was accompanied by a decrease in cytotoxic T cell effector gene expression. Additionally, CDKN2A expression was strongly up-regulated in the stroma and down-regulated 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.