Table 1.
Strategies to reverse T cell exhaustion
| Disease types | Intervention methods | Target | References |
|---|---|---|---|
| HIV | Anti-PD-L1 | PD-1 | [30] |
| HBV | Anti-PD-L1 | PD-1 | [31] |
| LCMV | Anti-PD-L1, anti-LAG-3 | PD-1, LAG-3 | [32, 33] |
| HIV | Knock-down of PD-L1 and PD-L2 | PD-L1, PD-L2 | [34] |
| HIV | Anti-CTLA-4 | CTLA-4 | [36] |
| HBV | Anti-CTLA-4 | CTLA-4 | [37] |
| Bladder cancer | Anti-CTLA-4 | CTLA-4 | [38] |
| LCMV | Anti-TIM-3 | TIM-3 | [39] |
| HCV | Anti-TIM-3 | TIM-3 | [42] |
| HIV | Anti-TIM-3 | TIM-3 | [43] |
| HCC | Anti-TIM-3 | TIM-3 | [45] |
| LCMV | Anti-LAG-3 | LAG-3 | [46] |
| RCC | Knock out of VISTA | VISTA | [49, 50] |
| HCV | Anti-PD-L1, anti-CTLA-4 | PD-1, CTLA-4 | [51] |
| HBV | Anti-PD-L1, anti-CTLA-4 | PD-1, CTLA-4 | [52] |
| LCMV | Anti-PD-L1, anti-TIM-3 | PD-1, TIM-3 | [53] |
| GC | Anti-PD-1, anti-PD-L1, anti-LAG-3, anti-TIM-3 | PD-1, TIM-3, LAG-3 | [54] |
| Osteosarcoma | Knockout of DNMT3A | DNMT3A | [56, 57] |
| LCMV | Knockout of TOX | TOX | [58] |
| Melanoma | Knockout of TOX | TOX | [59] |
| LCMV | Knockout of NR4A1 | NR4A1 | [61, 62] |
| LCMV | Knockout of Eomes | Eomes | [66] |
| LCMV | Knockout of T-bet | T-bet | [67] |
| CLL | BTK inhibitor | Glycolysis | [72] |
| LCMV | Anti-PD-L1 | Glycolysis | [73] |
| Sarcoma | Anti-PD-1, anti-PD-L1, anti-CTLA-4 | Glycolysis | [75] |
| NSCLC | Anti-PD-1 | Glucose, lipid and mitochondrial metabolism | [76] |
| Melanoma | Knock down and overexpress of XBP1s | Cholesterol | [77, 78] |
| Lymphoma | Glutamine metabolism inhibitors | Glutamine metabolism | [79] |
| Breast cancer, cervical cancer | D-1MT | Tryptophan catabolism | [81] |
| HBV | Anti-CD3, and anti-CD28 | Arginine | [82] |
| HIV | IL-15 | Glycolysis | [84] |
| HCV | Histone methyltransferase inhibitors | Glycolytic and mitochondrial functions | [85] |
| Colon cancer, lymphoma, melanoma | DON, JHU083 | Glutamine | [87] |
| HBV | Mitochondrion-targeted antioxidants | Mitochondria | [86] |
| ccRCC | Metformin | Mitochondrial ROS | [89] |
| Melanoma | Axitinib, anti-PD-1, anti-CTLA-4 | Mitochondrial ROS | [91] |
| Melanoma, lung cancer, colorectal cancer | Overexpress of PGC1α | Mitochondrial metabolism | [92] |
| LCMV, melanoma | Knock out of VHL | HIF-1α, HIF-2α | [94] |
| Breast cancer | Knock out of HIF-1α | HIF-1α, VEGF-A | [95] |
RCC renal cell carcinoma, GC gastric cancer, CLL chronic lymphocytic leukemia, BTK Bruton’s tyrosine kinase, d-1MT 1-methyl-d-tryptophan, NSCLC non-small-cell lung cancer, IL-15 interleukin-15, DON 6-diazo-5-oxo-l-norleucine, ccRCC clear cell renal cell carcinoma