Figure 1.

Schematic representation of the contribution of the immune system in the dysplasia to carcinoma sequence in IBD-associated cancer. Chronic inflammation promotes the recruitment of immune cells into the intestinal mucosa of inflammatory bowel disease (IBD) patients. These cells will secrete pro-inflammatory cytokines such as tumor necrosis factor alpha (TNF-α), interleukin (IL) -6 and IL-1β. In addition, these tissue-infiltrating cells produce oxidative compounds including reactive oxygen species and reactive nitrogen species, generating tissue injury and DNA damage, promoting excessive epithelial cell proliferation and favoring genomic aberrations and genetic mutations. TP53 mutations result in low-grade dysplastic mucosa, after which mutations in KRAS are considered to be involved in progression from low-grade dysplasia to high-grade dysplasia. Finally, mutations in the APC gene result in cancer. Chronic inflammation also induces immunosuppressive mechanisms that may be involved in cancer progression, such as recruitment of M2 macrophages, T regulatory cells (Tregs) or T lymphocytes expressing inhibitory markers; programmed cell death protein 1 (PD-1), cytotoxic T-lymphocyte-associated protein 4 (CTLA-4). In addition, there is an increase in angiogenic factors and anti-inflammatory cytokines; IL-10 and transforming growth factor beta (TGF-β) which favor carcinoma development. (Tol-Dendritic cells: Tolerogenic dendritic cells, ROS: reactive oxygen species, RNS: reactive nitrogen species).