Table 1 Strategies for targeting immunosuppressive cell metabolism for cancer therapy.
From: Metabolic adaptations of immunosuppressive cells in cancer: mechanisms and therapeutic targets
Metabolic vulnerability | Target | Drug(s)/targeting method(s) | Indication(s) | Notes | Clinical status | Reference |
|---|---|---|---|---|---|---|
Fatty acids | FATP2 | Lipofermata | MDSCs TANs | Decreased Lipid/ROS accumulation; reduced tumor growth; synergized with ICB | Preclinical | |
CPT1 | Etomoxir | TAMs Treg cells | Inhibited lipid metabolism (FAO); M1-like TAM reprogramming and reduced Treg suppressive function; high-dose off-target effects | Preclinical | ||
SLC3A2 | CRISPR/Cas9 | TAMs | Inhibited M2 macrophage polarization | Preclinical | ||
Glucose | mTOR | Rapamycin | MDSCs | Reduced tumor growth | Phase I/II NCT01195922 | |
Glycolysis | 2-DG | TAMs Tregs | Inhibited M2 macrophage polarization; decreased Treg function and proliferation | Phase I/II NCT00633087 | ||
Glycolysis | Galloflavin | Treg cells | Decreased Treg function and proliferation; | Preclinical | ||
Amino acid | ARG1 | CB-1158, INCB001158 | MDSCs | Enhanced antitumor immune responses; synergized with ICB | Phase I NCT02903914 | |
GS | MSO | TAMs | Promoted M1 macrophage polarization | Preclinical | ||
Lactate | LDHA | Oxamic acid | TAMs | Reduced lactate production; attenuated M2 macrophage polarization; prevented disease progression | Preclinical | |
Energy metabolism | AMPK | RA | TANs | Reduced tumor growth | Phase II NCT02403778 | |
Kynurenine | IDO1 | Epacadostat | Treg cells | Preclinical studies showed inhibition of Treg-mediated immunosuppression; no clinical benefit was observed in phase III trials when combined with anti-PD-1 therapy | Phase III NCT02752074 |
