Fig. 3

Targeting multiple metabolic pathways of mitochondria can enhance the anti-tumor effect of CD8+ T cells. (The red arrows indicate promotion, and the green arrows indicate inhibition) ①Activating CD28, increasing enolase 1 activity, or adding exogenous pyruvate and PEP can promote the glycolysis of CD8+ T cells. ②Inhibiting LDH activity and supplementing exogenous L-arginine can promote OXPHOS of CD8+ T cells. ③For melanoma, fibrosarcoma, colon cancer and lung cancer, a combination of bezafibrate with PD-1 blockade can promote FAO and function of CD8+ T cells, while inhibiting FAO can improve the anti-tumor effect of CD8+ T cells in breast cancer. ④Up-regulating the expression level of transcriptional activity of PGC1-α in CD8+ T cells can facilitate mitochondrial biogenesis and functional recovery. It can be achieved by stimulating 4-1BB combined with PD-1 blockade, inhibiting the activity of Akt, inhibiting the mTORC2 pathway to activate Foxo1, and using nicotinamide adenine dinucleotide to activate SIRT1. ⑤Regulating mitochondrial fusion and fission by essential GTPase (Drp1, Mfn1, Mfn2 and Opa1) can control CD8+ T cell function. ⑥MAPK/ERK can prevent the release of cytochrome C from mitochondria to cytoplasm and the activation of caspase cascade, decreasing CD8+ T cell apoptosis. ⑦Addition of BH4 can regulate mitochondrial iron transport and respiration in CD8+ T cells, increasing the activation of CD8+ T cells