Table 1.
The immunoregulatory agents target MDSCs within the TME.
| Tumor types | Agents | Mechanisms/Functions | Advantage | Disadvantage | Reference |
|---|---|---|---|---|---|
| 4T1 breast cancer (mouse model) | Docetaxel | To polarize MDSC differentiation into M1-like macrophages through the reduced phosphorylation of STAT3. | Direct effect of chemotherapeutic agents on tumor and tumor MDSCs | N/A | (30) |
| In vitro MDSC culture model | Paclitaxel | To promote MDSC differentiation into DCs, | Ultra-low non-cytotoxic doses of paclitaxel induces MDSC differentiation | N/A | (31) |
| Breast/colonic cancer; renal carcinomas (mouse models) | Sunitinib | To reduce the number of MDSCs through inhibition of STAT3 signal. | To target both cancer cells and MDSCs | N/A | (32) |
| Renal cell carcinoma (patients) | Sunitinib | Blockade of VEGF and c-KIT signal | To diminish the number of both MDSCs and Treg cells | No correlation between a change in tumor burden and a change in MDSCs/Treg | (33) |
| Melanoma (mouse model) | DATS | To abrogate number and immunosuppressive activity of MDSCs. | To improve T cell anti-tumor response. | N/A | (34) |
| CLL (mouse model) | Vitamin D | To downregulate MDSC function as negative regulator of miR155. | To easily enhance anti-tumor activity | N/A | (35) |
| Gastric/colonic cancer (mouse models) | Curcumin | To inhibit the functions of MDSCs by the inactivation of STAT3 and NF-kB signaling | To interfere with the interaction between cancer cells and MDSCs | N/A | (7) |
| Head/neck squamous cell carcinoma (patients) | Tadlafil | Inhibitors of PDE5. To inhibit the activity of iNOS and Arg-1to reduce both MDSCs and Treg concentrations | To promote the activation of CD8+ T cells at the tumor site | Grade 1–3 adverse events (such as back pain/myalgia) | (36) |
| Pancreas/lung cancer (mouse models) | Entinostat | To neutralize MDSCs through reduced expression of Arg-1, iNOS, and COX2. | To enhances the antitumor effect of PD-1 | N/A | (37, 38) |
| NSCLC (patients) | JNJ-61610588 | Anti-VISTA monoclonal antibody | To inhibit the function of both Treg cells and tumor MDSCs | To induce autoimmunity | (39) |
| Metastatic melanoma/breast cancer/NSCLC (patients) | Pembrolizumab | PD-1blocker | To inhibit both tumor and tumor MDSCs | To induce pneumonitis | (40) |
| Melanoma (patients) | Nivolumab Lambrolizumab | Monoclonal antibodies targeting PD-1 | To result in a high rate of sustained tumor regression | Grade 1-2 toxic effects (including diarrhea, nausea) | (41, 42) |
| Metastatic urothelial carcinoma (patients) | Atezolizumab | PD-L1 monoclonal antibody | To inhibit PD-L1 positive cells (tumor cells and MDSCs) | Grade 3–4 adverse events (including pneumonitis/fatigue) | (43) |
| Metastatic melanoma (patients) | Ipilimumab | Human monoclonal antibody against CTLA-4 | To boost the body’s immune response against cancer cells | To induce diarrhea | (44) |
CLL, chronic lymphocytic leukemia; APCs, antigen-presenting cells; DATS, diallyl trisulfide; DCs, dendritic cells; PDE5, phosphodiesterase-5; N/A, not available; TME, tumor microenvironment; NSCLC, non-small cell lung cancer.