Immunometabolism: A novel perspective of liver cancer microenvironment and its influence on tumor progression

Table 1 Immunometabolic therapies for cancers

Targets	Agents	Mechanisms	Developments
PKM2	DASA, TEPP46	Inhibition of HIF1α	Preclinical
HIF1α	PX-478, RO7070179, EZN-2968	Inhibition of HIF1α	Phase 1
PTEN	VO-Ohpic, SF1670	Inhibition of PI3K	Preclinical
PDK	Dichloroacetate	Inhibition of glycolysis	Phase 2
GLUT1	Ritonavir	Inhibition of glycolysis	FDA-Approved
LDH	Gossypol (AT-101), FX11, Galloflavin	Inhibition of glycolysis	Phase 3
CPT1A	Etomoxir	Inhibition of FAO	Preclinical
CTLA-4	Ipilimumab	Checkpoint blockade; Inhibition of FAO	FDA-Approved
PD-1/PD-L1	Nivolumab, Pembrolizumab, Atezolizumab	Checkpoint blockade; Inhibition of FAO	FDA-Approved
AMPK	Metformin	Increased FAO; Inhibition of Complex I; Decreased mitochondrial ROS	FDA-Approved
mTOR	Temsirolimus, Everolimus	Inhibition of HIF-1α translation	FDA-Approved
IDO	Epacadostat	Regulation of tryptophan metabolism; Inhibition of mTORC1	FDA-Approved
IDH1/2 mutations	Ivosidenib (AG-120), IDH305, AG-881, DS-1001b	Inhibition of 2-HG production	Phase 3
FGFR	Regorafenib, Sunitinib, TAS120	Inhibition multi-targeted kinase	Phase 2
iNOS	L-NMMA, 1400W	Inhibition of NO production	Phase 2
FOXP3	P60	suppress NF-κB and NFAT	Preclinical

PKM2: Pyruvate kinase M2; HIF: Hypoxia inducible factor; LDH: Lactate dehydrogenase; FAO: Fatty acid oxidation; CTLA-4: Cytotoxic T-lymphocyte-associated protein 4; mTOR: Mammalian target of rapamycin; FGFR: Fibroblast growth factor receptor; FoxP3: Forkhead box P3; ROS: Reactive oxygen species.