Hallmark of Cancer: Avoiding immune destruction through non-genotoxic carcinogens (Homo sapiens)
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Description
The non-genotoxic carcinogens include ROS, divided by it’s origin, and factors released by surrounding cells. As the monocytic myeloid-derived suppressor cells (MDSC) are key component in permitting the evasion from the immune system they are placed mostly centrally. The components placed on the external wall of the represented cells are membrane bound receptors. The general processes of expansion, proliferation and apoptosis are shown in the relevant cells. In the case of the transformation of metabolites (tryptophan to kynurenine and arginine to urea) it is the depletion of the first metabolite that leads to the effect shown by the arrows. The inhibitory pathways for the immune system are through inactivation of the cytotoxic T-cells and the activation of regulatory T-cells (which have an immunosuppressive role). To achieve the tumour cells, transform present immune cells into MDS cells, mostly done by cancer associated fibroblasts which release CCL2. Furthermore, MDSCs can also by recruited to the tumour environment through the release of many cytokines. To inhibit the cytotoxic T-cells, many mechanisms are exploited. One of which is stopping the T-cell from binding through the inhibition of the major histocompatibility complex (MHC) and the inhibition of the phosphorylation of the linker for activation of T-cells (LAT), the carcinogens can also directly inhibit the phosphorylated LAT. Another mechanism is to trigger the apoptotic pathway in the cytotoxic T-cells. Additionally, certain carcinogens inhibit the proliferation of the T-cells. Lastly, regulatory T-cells and some molecules can directly inhibit the T-cells.
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