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. 2023 Jul 10;14:1210164. doi: 10.3389/fimmu.2023.1210164

Figure 3.

Figure 3

Postulated mechanisms by which MSI-H tumors evade immune recognition during development and following ICB. (A) LS-associated polyps initially have low mutational and neoantigen burden. Immunoediting of quality (immunogenic) neoantigens with low and/or subclonal expression and impaired antigen presentation may lead to immune evasion in developing tumors. (B) LS associated polyps display an immune activation profile characterized by CD4 T cells, proinflammatory cytokines (TNF, IL-12), and CTLA-4, LAG3 and PD-L1 checkpoints. They progressively develop additional mutations and high TMB, which is characterized by T cells entering an exhaustion state. It may also involve an IFN-induced expression of HLA-E that inhibits CD8+ T cells and NK cells via the NKG2A/CD94 receptor. (C, D) MSI-H tumors can develop strong anti-tumor immune responses as well as developing immune suppressive inflammatory hubs that compromise anti-tumor immunity (47). In human MSI-H tumors, an inflammatory hub populated by inflammatory Tregs (C), MMP-expressing CAFs (D), monocytes, and neutrophils may further increase immune escape during MSI-H tumor development, promoting tumor angiogenesis and tissue remodeling (47). (Created with BioRender.com).