Studies and strategies targeting the MDSC-Arg1 pathway
| Study | Cancer type | Strategy to suppress MDSC function |
|---|---|---|
| Ding et al. [39] | Colon cancer | IPI-549 inhibits PI3Kγ in MDSCs leading to downregulation of Arg1 and ROS, and promote MDSC apoptosis. The resultant activation of CD8+ T cells reduced tumour recurrence and metastasis. |
| Yu et al. [113] | Hepatocellular carcinoma (HCC) | Treatment with PDE5 inhibitor suppressed MDSC immunosuppressive functions via inhibiting Arg1 and iNOS in HCC models. |
| Yuan et al. [47] | Lung cancer | Addition of anlotinib to radiotherapy and anti-PD-1 treatment reduced MDSCs and Arg expression leading to enhanced CD8+ T cell infiltration and IFNγ production. |
| Wang et al. [44] | Multiple cancer types | P300-mediated C/EBPβ acetylation enhances MDSC Arg1 expression and immunosuppressive function. Pharmacological inhibition of P300 may be of benefit to target MDSCs although this was not formally tested in the study. |
| Wang et al. [35] | Diffuse large B-cell lymphoma (DLCBL) | In treatment-naive DLBCL adults, a high M-MDSC surface expression of TREM2 is a poor prognostic factor for both PFS and OS, highlighting TREM2 as a potential therapeutic target. |
| Khaki Bakhtiarvand et al. [48] | Breast cancer | Addition of cabozantinib to anti-HER2 treatment enhanced IFNγ levels and reduced tumour growth via inhibition of Arg1+ MDSCs. |
| Li et al. [41] | Lung cancer | Sanguinarine (SNG) treatment inhibits MDSC suppressive function via reducing Arg1, iNOS and ROS expression. |
| Zamani et al. [45] | Breast cancer | Doxorubicin chemotherapy reduced MDSC frequency, Arg1, iNOS and ROS expression, and enhanced anti-tumour T cell tumour infiltration. |
| Steggerda et al. [38] | Multiple cancer types | Arg inhibitor CB-1158 treatment inhibited MDSC-mediated T cell suppression leading to reduced tumour growth in multiple murine cancer models, either alone or in combination with immunotherapies such as immune checkpoint inhibitors, adoptive T cell or NK cell transfer and chemotherapy. |
| Wang et al. [42] | CRC (colitis-associated) | Blocking MyD88 with the novel inhibitor TJ-M2010-5 suppressed MDSC Arg1 and iNOS expression enhancing anti-tumour immunity. |
| Otvos et al. [46] | Gliobastoma | Depletion of Arg1+ MDSCs via blocking migration inhibitory factor (MIF) or through a low-dose 5-flurouracil (5-FU) regime resulted in prolonged survival in a mouse model of glioma. |
| Le Noci et al. [114] | Melanoma lung metastases | Nebulised anti-MDSC antibody RB6-8C5 treatment reduced mRNA levels of Arg1, leading to NK cell activation and enhanced tumour reduction. |
| Poon et al. [49] | CRC | Anti-CTLA-4 immune checkpoint inhibition increased Arg1 expression in the tumour microenvironment. The increase in Arg1 expression can be effectively reversed by combination treatment with selumetinib, the latter suppressing MDSCs, leading to potentiation and enhanced anti-tumour efficacy of immune checkpoint blockade. |
| Thakur et al. [50] | Pancreatic cancer | Combination treatment using anti-CD3 and anti-HER2 bispecific antibody together with EGFR inhibitor reduced MDSC Arg1 expression, leading to increased levels of Th1 cytokine-mediated anti-tumour immunity. |
PDE5: phosphodiesterase 5; C/EBPβ: CCAAT/enhancer-binding protein β; HER2: human epidermal growth factor receptor 2; MyD88: myeloid differentiation factor 88; mRNA: messenger RNA; CTLA-4: cytotoxic T-lymphocyte antigen-4; EGFR: epidermal growth factor receptor
