Figure 3.

Hypothesized model showing the development of two different immune evasion mechanisms in Lynch syndrome-associated colorectal cancer. When the baseline epithelial tissue is highly infiltrated with CD3 and CD8 T cells (in purple) (panel to the right), preliminary tumor cells (in green) are forced to evade the immune system at early stages. This could be done by loss of heterozygosity of B2M and subsequent loss of MHC class I receptors generating a new tumor variant (in blue). However, if the baseline epithelial tissue has a low infiltrative level of CD3 and CD8 cells (panel to the left), there will be no selective pressure on the early tumor cells to avoid the immune system. Nevertheless, the high mutation rate seen in Lynch syndrome tumors will eventually lead to extensive presentation of neoepitopes through MHC class I receptors, which will attract and activate cytotoxic T cells. To avoid immune-mediated killing the tumor cells may adapt and shield themselves through up-regulation of PD-L1 causing T cell exhaustion. TCR = T cell receptor.