From:  Metabolic mechanisms of immunotherapy resistance
 

Drugs for targeted metabolism combined with immunotherapy

DrugTargeted metabolismMechanismAppropriate immunotherapyReference
BicarbonateGlycolysisDirectly increase pH valueAnti-PD-1/L1/CTLA-4 treatment[107]
DiclofenacGlycolysisInhibit lactate transporter proteinAnti-PD-1/L1 treatment[108]
CB839GlutaminolysisInhibit GLS activityCAR-T cell therapy[69]
JHU083GlutaminolysisInhibit GLS activityAnti-PD-1/L1 treatment[119]
V-9302GlutaminolysisInhibit glutamine transporter proteinAnti-PD-1/L1 treatment[120]
Glycolytic metabolite phosphoenolpyruvate (PEP)GlycolysisSustaining NFAT signaling and T cell effector functions, and its enhancement in the TME has been shown to boost T cell activityAnti-PD-1/L1 treatment[109]
Methionine supplementationMethionine metabolismImproved the expression of H3K79me2 and STAT5 in T cells, and this was accompanied by increased T cell immunityAnti-PD-1/L1 treatment[117]
Chemotherapeutic prodrug (TH-302)Hypoxia-inducible factorThis approach reduces myeloid cell-mediated suppression and enhances the infiltration of effector T cellsAnti-PD-1/L1 treatment[116]
Arachidonic acidLipid metabolismIFN-γ in combination with arachidonic acid induces immunogenic tumor ferroptosis, serving as a mode of action for CD8+ T cell mediated tumor killingAnti-PD-1/L1 treatment[125]
AvasimibeLipid metabolismInhibition of ACAT1, a crucial enzyme involved in cholesterol esterification, resulted in enhanced effector functions and increased proliferation of CD8+ T cells, while having no significant effect on CD4+ T cellsAnti-PD-1/L1 treatment[124]
Return to article view

GLS: glutaminase; IFN-γ: interferon gamma; ACAT1: acyl-CoA acyltransferase 1; NFAT: nuclear factor of activated T-cells; TME: tumor microenvironment