Furthermore, the mechanism by which MDSCs regulate the conversion from IBD to CAC is largely unknown. 4 Currently, the functional and phenotypic heterogeneity of MDSCs leads to controversy about their role in IBD. In IBD and CAC, MDSCs massively infiltrate the inflamed intestinal tissue and tumor microenvironment and have been a research focus due to their roles in inflammation and tumorigenesis. 3 Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population of myeloid progenitors and immature myeloid cells. These myeloid cells play an important role in promoting the conversion of IBD to CAC. The lymphocytes further recruit myeloid cells into the local intestinal tissue. Dendritic cells (DCs) and macrophages sense invading micro-organisms and regulate the differentiation of proinflammatory lymphocytes such as T helper (Th1) cells, Th17 cells, innate lymphoid cells (ILCs), and interleukin (IL)-17 + γδT cells. The massive infiltration of myeloid cells and lymphocytes into the inflamed intestinal tissue is the main pathological feature of IBD.
#Task3 myeloid suppressor driver
However, the exact cause of chronic inflammation in patients with IBD and the key driver of the conversion from IBD to CAC still remain unknown. CAC provides a great model to understand the role of chronic inflammation in tumors. On the other hand, inflammation activates the Wnt/β-catenin signaling pathway, which induces intestinal epithelial cell (IEC) proliferation and remodeling and then promotes CAC development. 2 On the one hand, inflammation causes strong genotoxic reactions, such as DNA damage and mutations in important genes, which subsequently drive CAC initiation. 2 The cumulative risk for CAC in patients with CD has been reported to be 18.4% after 30 years of disease duration. A meta-analysis of 54 478 patients with UC, including 1698 cases of CAC, found that the overall prevalence of colorectal cancer (CRC) among UC cases was 3.7%. Inflammatory bowel disease (IBD), which is composed of Crohn’s disease (CD) and ulcerative colitis (UC), is the result of continuous microbial antigen-induced immune responses as a consequence of host genetic defects in intestinal mucosal barrier function, immunomodulation, or bacterial killing. 1 The etiology of CAC includes epigenetic changes, somatic mutations, and chronic inflammation. Colitis-associated cancer (CAC) follows the sequence of normal tissue, hyperplasia, high-grade dysplasia, and adenocarcinoma.
0 kommentar(er)
