Table 2 Macrophage metabolic targets and associated therapeutics in preclinical and clinical studies
Target | Drugs | Tumor type | TAM marker | Metabolism | Mechanism | Type of research/outcome | Ref. |
|---|---|---|---|---|---|---|---|
ETC | metformin | the lungs of 4T1 mammary carcinoma mice model | CD11c, CD163 | glycolysis, OXPHOS | lower intracellular ATP levels, inhibit the activity of mitochondrial respiratory chain chain, activate the AMPK pathway, promote glucose uptake and glycolysis | preclinical/positive | [174] |
ETC | metformin | human esophageal cancer | CD11c, CD163 | glycolysis, OXPHOS | lower intracellular ATP levels, inhibit the activity of mitochondrial respiratory chain chain, activate the AMPK pathway, promote glucose uptake and glycolysis | clinical trial phase II | [175] |
MARCO | MARCO inhibitors, ED31 | 4T1 mammary carcinoma, MC38 colon cancer carcinoma, the B16 melanoma model NCSLC lung carcinoma model | MARCO, CD68, MHC-II, TIE2 | glycolysis | enhance glycolysis | preclinical/positive | |
LXR/ABCA1 | the combination of simvastatin and paclitaxel | A549T lung carcinoma xenograft model | CD206, Arg1, TGF-β | cholesterol metabolism | affect LXR/ABCA1 regulation through cholesterol-related pathways | preclinical/positive | [178] |
TLRs | TLR 9 agonist, CpG oligodeoxynucleotides | PDAC mice model | CSF1R, Arg1, CD206, MHC-II | lipid metabolism | promote FAO, divert intermediates of the TCA cycle for de novo lipid synthesis | preclinical/positive | [179] |
GS | GS inhibitor, MSO | LLC lung cancer model | CD80, MHC-II, CD206, CD163 | glycolysis, glutamine metabolism | decrease glutamine, increase succinate levels, improve glucose flow via glycolysis | preclinical/positive | [154] |
IDO1 | IDO1 inhibitor, NLG919 | B16F10 melanoma model | CD206, CD163 | tryptophan metabolism | reverse the M2-like phenotype, the specific mechanisms have not been elucidated | preclinical/positive | [56] |
IDO1 | IDO1 inhibitor, epacadostat | human melanoma | CD206, CD163 | tryptophan metabolism | reverse the M2-like phenotype, the specific mechanisms have not been elucidated | clinical trial phase III (NCT02752074)/negtive | [180] |
Arg1 | Arg1 inhibitor, CB-1158 | 4T1 mammary carcinoma, LLC lung cancer, B16 melanoma, CT26 colorectal carcinoma model | CD68, CD80; CD206, Arg1 | argine metabolism | rise in CD80+ TAMs and decrease CD206+TAMs, the specific mechanisms have not been elucidated | preclinical/positive | [181] |
CD40 | agonistic anti-CD40 monoclonal antibodies, FGK45 | YUMM1.7 melanoma model | CD40 | FAO, glutamine metabolism | trigger FAO and glutamine metabolism, promote ATP citrate lyase-dependent epigenetic reprogramming of anti-tumorigenic phenotypes in TAMs, glutamine usage reinforces FAO-induced anti-tumorigenic activation | preclinical/positive | [182] |