Table 1.
Strategies for targeting immunosuppressive cells
| Characteristic | MDSCs | Tregs | TAMs | |||
|---|---|---|---|---|---|---|
| Deactivation | • | PDE5 inhibitor | ||||
| • | STAT3 oligonucleotide inhibitor | |||||
| • | HDAC inhibitor | |||||
| Differentiation | • | ATRA | ||||
| • | Derivative of vitamin A | |||||
| Blocking development | • | N-Bisphosphonate | ||||
| Depletion | • | Cytotoxic agents (gemcitabine, cisplatin, paclitaxel, or 5-FU or HSP90 inhibitor, 17-DMAG) | • | Fc-optimized anti-CD25 Ab | • | Liposome-encapsulated clodronate |
| Blockade of trafficking | • | PDE5 inhibitor | • | Anti-CCR4 Ab | • | Anti-CCR2 Ab |
| • | CCL2 neutralizing Ab | |||||
| Blocking Inhibitory Cytokines | • | Neutralization of IL-35 or Treg-specific deletion of IL-35 | ||||
| Reprogramming Polarization | • | Baicalin, a natural flavonoid | ||||
| • | CSF-1R inhibitor | |||||
| Blocking the downstream effect | • | Anti-IL-6 receptor Ab (tocilizumab) | ||||
| New systemic therapies (TKIs or ICIs) | • | Cabozantinib | • | Anti-PD-1 Ab | • | Lenvatinib |
| • | Agonistic TRAIL-R2 Ab | • | Anti-CTLA-4 Ab | • | VEGF inhibitor (bevacizumab) & anti-PD-L1 Ab (atezolizumab) | |
| • | Anti-GITR Ab | |||||
| • | Anti-OX40 Ab | |||||
MDSCs, myeloid-derived suppressor cells; Treg, regulatory T-cells; TAM, tumor associated macrophages; PDE, phosphodiesterase; STAT, signal transducer and activator of transcription; HDAC, histone deacetylase; ATRA, all-trans-retinoic acid; FU, fluorouracil; HSP, heat shock protein; DMAG, 17-dimethylaminoethylamino-17-demethoxygeldanamycin; TKI, tyrosine kinase inhibitor; ICI, immune checkpoint inhibitor; TRAIL, tumor necrosis factor-related apoptosis-inducing ligand; IL, interleukin; PD, programmed cell death protein; CTLA, cytotoxic T-lymphocyte-associated protein; GITR, glucocorticoid-induced TNFR family related gene; CCR, cell cycle-related kinase; CCL, C-C motif chemokine ligand; CSF, stimulating factor; VEGF, vascular endothelial growth factor; TNFR, tumor necrosis factor receptor.