Table 2.

Key gene targets of MYC in cancer metabolism and oncoimmunology.

Gene Target	Main Hallmark	Role in Oncometabolism	Role in Oncoimmunology	Reference
LDHA	Metabolism	Required in the production of lactate in anerobic glycolysis.	Inhibits immune killing and promotes immunosuppression by increasing lactate production and influencing the microenvironment. Negatively regulates immune infiltration.	(92) (134, 135)
GLUT1	Metabolism	A glucose transporter responsible for the uptake of glucose into cells.	Associated with increases in neutrophil, platelet, monocytes, and lymphocyte count. Negatively correlates with tumor-infiltrating T -cells but positively correlates with neutrophils and dendritic cells	(90, 136, 137)
ENO1	Metabolism	Responsible for converting 3’ biphosphoglycerate to 3’biphosphopyruvate	Promotes anti-tumor immunity by promoting PD-L1 proteolysis.	(90, 138)
SLC1A5	Metabolism	Glutamine Transporter	Overexpression is associated with the presence of immunosuppressive immune cells such as CD68+ macrophage, FOXP3+ regulatory T cells, CD20+ B cells, and PD1+ lymphocytes. SLC1A5 is also required for MYC induction of cytokine-stimulated NK cells.	(84) (139)
SLC38A5	Metabolism	Glutamine Transporter and amino acid coupled Na+/H+ exchanger	Maintains extracellular acidification while maintaining intracellular pH. Acidification of the microenvironment turns off? anti-tumor lymphocyte function.	(140, 141)
IL-23	Immunology	When secreted by tumor-associated macrophages it Interlinks glutamine addiction and immune evasion in kidney cancer.	Cytokine that recruits pro-tumoral macrophages	(111, 142)
CD47	Immunology	Tumor intrinsic CD47 regulates glycolysis in colorectal cancer cells by stabilizing ENO1.	Inhibitory Immune Checkpoint Molecule which turns off immune response in NK and T cells	(143, 144)
PD-L1	Immunology	Regulates glycolysis by improving PFKFB3 expression in renal cell carcinoma cells.	Inhibitory Immune Checkpoint Molecule which turns off immune response in NK and T cells	(143, 145)
VEGF	Immunology	Exogenous VEGF alters metabolism of triple negative breast cancer cells by modulating MAPK-ERK and PI3K-AKT pathways	An immunosuppressive growth factor that impedes the development of T cells and impairs maturation of dendritic cells.	(146–149)
HIF1A	Immunology	Transcribes genes that encode glycolytic enzymes (such as HK2, TPI, ENO1, and PKM) and glutamine metabolism.	Produces IL-9 during TH9 differentiation involved in pro-inflammatory signaling and anti-tumor immunity. HIF1A also partners with mTOR to promote CD8 memory T cell generation. HIF1A also upregulates PD-L1 on tumor cells.	(125, 150–152)
STING	Immunology	STING driven interferon signaling drives metabolic reprogramming of pancreatic cancer cells.	STING induced interferon signaling is crucial in inducing anti-cancer immune response. STING activation enhances antigen presentation and therefore activation of T cells.	(153–155)
TGFB	Immunology	Canonical signaling of TGF-β modulates metabolic reprogramming by upregulating genes involved in glycolysis and oxidative phosphorylation.	TGF-β is a cytokine that promotes cancer progression by impairing T cell proliferation and expansion. TGF-β in cancer associated fibroblasts also promotes immune evasion through ECM signaling.	(156–158)