From: Optimizing CAR-T cell therapy for solid tumors: current challenges and potential strategies
Effects | Biomarker | Signaling pathways and metabolic mechanisms |
---|---|---|
CAR-T cell activation | 1. SHP-1 | 1. TNF-α, IL-2, IFN-γ secretion |
CAR-T cell proliferation | 1. PD-L1 2. IL-18 | 1. PD1/PD-L1 pathway 2. IL-13, IFN-γ secretion |
CAR-T cell cytotoxicity | 1. B7-H3 2. tmTNF-α 3. CD40L 4. MSLN 5. TREM2 6. IL-4/15 7. IL-12 8. PIK3C 9. PIK3R3 10. NAD | 1. B7-H3/ B7-H3 ligand 2. NTF-ERK-GST, NTF-NF-κB 3. CD40/CD40L 4. AKT, ERK1/2, JNK 5. RAS/MEK/ERK 6. AKT, JAK/STAT, IFN-γ secretion 7. IL-17, IFN-γ secretion 8. PI3K/AKT 9. PI3K/AKT 10. NAD + salvage pathway |
CAR-T cell exhaustion and differentiation | 1. PRDM1/NR4A3 2. FOXO1 3. NOTCH1 4. Cbl-b 5. TET2 6. PRODH2 7. SphK1 | 1. PRDM1/NR4A3/TCF7 2. AKT,MAPK 3. NOTCH-FOXM1 4. TCR/Cbl-b/STAT 5. c-MYC, mTORC1 6. Proline metabolism 7. Lipid metabolism |
Tumor cell proliferation | 1. LunX 2. CLDN6 3. EphA2 4. VEGFR-2 5. Glutamine 6. INO1 | 1. ERK, JNK pathway 2. STAT3 3. AKT, ERK1/2 4. VEGF/VEGFR 5. Glutamine/polyamine/hypusine 6. Glutamine/polyamine |