Table 2

Possible therapy strategies for CAC based on MDSC regulation

StrategiesEventsSubsetsModelsReferences
GemcitabineReduce intratumoral MDSCs.MDSCsmHer2/CT-26-bearing mice 92
Oxaliplatin and IL-12Reduce intratumoral MDSCs.MDSCsMC-38 liver metastasis model 93
5-FU, oxaliplatin, and bevacizumabDecrease G-MDSCs in the peripheral blood.G-MDSCsPatients with mCRC 94
5-FU, folinic acid, bevacizumab, and anakinraDecrease M-MDSCs in the peripheral blood.M-MDSCsPatients with mCRC 95
5-FC and Toca 511Decrease MDSCs in both the liver and brain.MDSCsCT-26 liver and brain metastasis model 96
Anti-SEMA4D Ab (VX15/2503)Inhibit MDSC expansion.MDSCsPatients with mCRC 101
Anti-cKit AbPrevent MDSC accumulation through blocking cKit-SCF interactions.MDSCsMCA-26-bearing mice 102
Anti-CCR2 AbBlock radiation-induced MDSC infiltration.M-MDSCsMC-38-bearing mice 103
OX40 agonistReduce intratumoral MDSCs.MDSCsCT-26-bearing mice 104
PembrolizumabPatients with MSI-H+ CRC 105
NivolumabPatients with MSI-H+ mCRC 106
RadiationReduce intratumoral MDSCs.MDSCsCT-26 and MC-38-bearing mice 117
NitroaspirinDecrease the recruitment or survival of intratumoral MDSCs, and Arg-1, NOS2, PNT expression.MDSCsCT-26-bearing mice 118
PDE-5 inhibitors
(sildenafil and tadalafil)
Decrease the recruitment of intratumoral MDSCs and Arg-1, NOS2 expression.G-MDSCsCAC mice 107
TriterpenoidsInhibit ROS expression.MDSCsMC-38-bearing mice 108
EtomoxirBlock the immunosuppressive functions of MDSCs.MDSCsMC-38-bearing mice 109
GSK872Reduce circulating MDSCs by inhibiting RIPK3 signaling.MDSCsAPCmin/+ mice,
MC-38-bearing mice
110
MetforminInhibit the immunosuppressive functions of G-MDSCs by reducing p-STAT3 levels.G-MDSCsCT-26-bearing mice 111
FluconazoleDecrease MDSC accumulation.MDSCsCAC mice 50
TFF2Arrest MDSC proliferation.MDSCsCAC mice 22
EZH2 inhibitorPromote MDSC generation from progenitor cells during IBD.MDSCsCAC mice 89
JugloneDecrease MDSC accumulation.MDSCsCT-26-bearing mice 112
HyperoxiaSuppress G-MDSC-derived exosome production.G-MDSCsCAC mice 12
  • Ab, antibody; Arg-1, arginase 1; CAC, colitis-associated cancer; CCR2, chemokine (C-C motif) receptor 2; c-Kit, cellular kit proto-oncogene; EZH2, enhancer of zeste homolog 2; 5-FC, 5-fluorocytosine; 5-FU, 5-fluorouracil; G-MDSCs, granulocytic MDSCs; IBD, inflammatory bowel disease; IL, interleukin; mCRC, metastatic colorectal cancer; MDSCs, myeloid-derived suppressor cells; M-MDSCs, monocytic MDSCs; MSI-H, microsatellite instability-high; OX40, oxford 40; PDE-5, phosphodiesterase 5; PNT, peroxynitrite; RIPK3, receptor interacting protein kinase 3; ROS, reactive oxygen species; SEMA4D, semaphorin 4D; STAT3, signal transducer and activator of transcription 3; TFF2, trefoil factor 2.