Fig. 3: A hostile immunosuppressive tumor microenvironment occurs secondary to tumorigenic mutations.
From: The therapeutic implications of immunosuppressive tumor aerobic glycolysis
High levels of nuclear myc and HIF increase tumor cell glycolysis, resulting in a TME rich in immunosuppressive molecules. Lactate is produced as a byproduct of oncogene activation. This transcriptional program also decreases the intratumor pH, increases the secretion of suppressive cytokines such as VEGF, recruits suppressive myeloid cells via G-CSF and promotes the extracellular degradation of ATP into adenosine. The combination of these metabolic perturbations and microenvironmental changes decreases the ability of the antitumor immune compartment to perform is requisite functions (seen as fewer cytokines and granzymes in antitumor CD8 + T cells and NK cells). This oxidative microenvironment creates a niche where Tregs, lipid-filled tolerogenic DCs, and suppressive myeloid cells thrive, thus promoting immune evasion and tumor progression.
