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. 2021 Aug 10;12:717850. doi: 10.3389/fimmu.2021.717850

Figure 2.

Figure 2

Impact of some secreted molecules in the TME on the expression of immunocheckpoints in T cells. The most common immune checkpoints on T cells include programmed death 1 (PD-1), cytotoxic T lymphocyte antigen 4 (CTLA-4), T cell immunoglobulin and mucin-3 (TIM-3), T cell immunoglobulin and ITIM domain (TIGIT) and lymphocyte activation gene 3 (LAG3), which interact with their ligands on tumor cells. IFNγ release by activated T cells induces PD-L1 up-regulation in tumor cells. TIM-3 interaction on Th1 cells with Galectin-9 (Gal-9) on tumor cells inhibits Th1 cell responses. Soluble HLA-G released by tumor cells up-regulates PD-1, CTLA-4, and TIM-3, on T cells. CD155 (PVR), and the Nectin family are ligands of TIGIT. Soluble PVR is released by tumor cells. Soluble Nectins released by cancer cells mediate transendothelial migration of immune cells promoting angiogenesis. HLA-II over-expression by tumor cells and fibrinogen-like 1 (FGL1) secreted by tumor cells impact the expression of LAG-3 in T cells.