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Fig. 5 | Cell & Bioscience

Fig. 5

From: Microglia and macrophage metabolism: a regulator of cerebral gliomas

Fig. 5

Therapeutic strategies targeting metabolism between GAMs and Gliomas. a Therapeutic strategies targeting arginine metabolism. ADI-PEG20, an arginine consumer, decomposes arginine in the TME, and induces upregulation of NOS2 expression and downregulation of Arg1 to promote M1-like polarization. In addition, ADI-PEG20 enhances the phagocytic ability of GAMs, and promotes the M1-like factors secretion. b Therapeutic strategies targeting tryptophan metabolism. Endogenous tryptophan metabolites and the NAD+ precursor quinolinic acid render gliomas resistant to radiotherapy and chemotherapy. Alkylating agents may alleviate therapeutic resistance by depleting intracellular NAD+. c Therapeutic strategies targeting glucose metabolism. HOE-642, an inhibitor of NHE1, significantly promotes infiltration of GAMs and T cells, upregulates mitochondrial OXPHOS pathway genes, enhances mitochondrial activity in immune cells, and diminishes glycolysis in GAMs and T cells. d Therapeutic strategies using microglia-derived sEV. Microglia-derived sEV carrying miR-124 alters the metabolism of glioma cells and reduces the release of lactate, NO and glutamate. In addition, sEV increases the expression of Glu transporter Glt-1 in astrocytes. e Therapeutic strategies targeting lipid metabolism. NR4A2 or SQLE inhibitors suppress tumor growth and reversed CD8+ T cell exhaustion. NR-encased hydrogel system and oncolytic adenovirus loaded with ApoA1 activate anti-tumor immunity through targeting the disordered cholesterol metabolism in GBMs. NOS2, nitric oxide synthase 2; NO, nitric oxide; Arg1, arginase 1; Trp, tryptophan; TDO, tryptophan-2,3-dioxygenase; 3-HA, 3-hydroxyanthranilic acid; 3-HAO, 3-hydroxy-anthranilic acid oxygenase; QPRT, quinolinic acid phosphoribosyl transferase; NHE1, Na/H exchanger isomer 1; OXPHOS, oxidative phosphorylation; sEV, small extracellular vesicles; Glt-1, glutamate transporter type 1; NR4A2, nuclear receptor subfamily 4 group A member 2; SQLE, squalene monooxygenase; ApoA1, apolipoprotein A1; DHCR7, 7-dehydrocholesterol reductase

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