Table 1.
The phenotype markers and functional characteristics of MDSCs as published in various studies on human CRC.
Orgin/Tumor stage | Phenotype | Suppressive activity | References |
---|---|---|---|
Circulating/I-IV | Lin− HLA-DR− CD11b+ CD33+ CD13+ CD115low CD117low CD124low CD14− CD15− CD66b− CD34− CD39+ CD73− PD-L1low PD-L2− PD-1− | MDSCs correlate with tumor metastasis. Inhibition of CFSE-labeled autologous CD3+ T cell proliferation at 2:1 ratios with MDSCs in the absence or presence of CD3/CD28 antibody stimulation for 3 days. | (26) |
CD33+ from PBMC were co-cultured with SW480/SW620 cells to induce tumor MDSCs | CD33+ CD11b+ HLA-DR−, CD14+ CXCR4+ CD39+ ARG-1+ iNOS+ ROS+ PD-L1+ CD73− CD117+/− CD34+/− CD66b+/− CD15weak | Tumor-induced MDSCs promoted SW480 and SW620 cell growth in a co-culture system in vitro. Tumor-induced MDSCs suppressed the proliferation of PBMCs labeled with CFSE more strongly than CD33+ cells cultured in medium alone. | (70) |
Circulating/tumor tissue | CD33+ CD11b+ HLA-DR− CD14+ CXCR4+/− CD39+/− ARG-1+ iNOS+ PD-L1+ ROS+ CD73− CD117+/− CD34+/− CD66b+/− CD15weak MDSCs from tumor tissue have higher PD-L1 expression | Advanced disease stage was associated with an elevated level of circulating MDSCs; also, tumor resection reduces the level of circulating MDSCs and Tregs measured 7 days after surgery. | |
Circulating/IV | CD14+ HLA-DR−/low S100A9high iNOS+ | – | (71) |
Circulating/tumor tissue/III IV | CD124+CD14+ CD124+CD15+ tumor tissue CD15+ CD14+ | Mixed lymphocyte reactions in which gamma-irradiated PBMC, CD14+, CD14−, and PMN from CRC patients were added as stimulator to responder PBMC derived from healthy donors. These experiments showed two main subpopulations with suppressive activity present among CD14+ monocytes in one and among PMN in the other. | (93) |
Colorectal tumor/III | PMN-MDSCs CD45+ Lin− HLA-DR− CD11b+ CD33+ CD66b+ Mo-MDSCs CD45+ Lin− HLA-DR− CD11b+ CD33+ CD14+ | PMN-MDSCs isolated from tumor inhibited the proliferation of activated autologous CFSE-labeled T cells and IFN-γ production in medium containing CD3 and CD28. | (94) |
Circulating | CD33+ HLA-DR− CD11b+ CD15+ CD33+HLA-DR−CD11b+CD15− CD33+HLA-DR−/lowCD14+ | Upregulated plasma levels of IL-6 and IL-10, where IL-6 correlates with 15+ MDSCs and IL-10 with 15− MDSCs. Also, CD15+ and CD15− MDSCs correlated with reduced IFN-α responsiveness in CD4+ T cells. | (95) |
Circulating/Metastasis | PMN-MDSCs CD33+ HLA-DR−/low CD15+ CD124+ PD-L1+ CD73+ CD39+ Mo-MDSCs CD33+ HLA-DR−/low− CD14+ PD-L1+ CD73+ CD39+ | Accumulation of PMN-MDSCs was associated with poor prognosis; also, PMN-MDSCs have higher levels of PD-L1, CD39, and CD73 expression and a stronger immunosuppressive function than Mo-MDSCs. Reduced TNF-α production and Ki67 proliferation marker of CD3+ T cells, especially by PMN-MDSCs. | (89) |
Circulating/I-IV | CD33+ CD11b+ HLA-DR−/low CD15−CD14+ ARG-1+ CD33+ CD11b+ HLA-DR− CD15+ CD14−ARG-1++ | – | (96) |
Tumor tissue/I-IV | CD33+ CD11b+ HLA-DR−/low CD15−CD14+ ARG-1+ CD33+ CD11b+ HLA-DR− CD15+ CD14−ARG-1+ CD33+ CD11b+ HLA-DR− CD15− CD14− | – | |
Circulating | PMN-MDSCs CD14−CD33+HLA-DR−CD66b+ | Human MDSCs increase fatty acid uptake and expression of FAO-related enzymes, and, in mice, inhibition of FAO blocked the tolerogenic function and immunosuppressive mechanisms of MDSCs. Inhibition of CFSE-labeled CD3+ T-cell proliferation after co-culturing with MDSCs from mice in the presence of anti-CD3. | (86) |
Circulating | Mo-MDSCs CD14+HLA-DR−/lo PMN-MDSCs CD33+ CD11b+ CD14− CD15+ SSChi | Mo-MDSC population was significantly expanded in CRC patients; the immunosuppressive capacity of these cells was evaluated in a T-cell suppression assay using a 3-way allogenic mixed leukocyte reaction (MLR). | (92) |
Circulating/cancer and adenoma | Total MDSCs: CD11b+HLA-DR−/low CD33+ PMN-MDSCs: CD11b+HLA-DR−/low CD33+ CD15+ CD14− Mo-MDSCs: CD11b+HLA-DR−/low CD33+ CD15− CD14+ e-MDSCs: CD11b+HLA-DR−/low CD33+ CD14− CD15− | PMN-MDSCs are the main immunosuppressive population, as depletion of CD15+ cells spares Mo-MDSCs and eliminates most of the suppression of T-cell proliferation and interferon production. MDSC levels negatively correlated with anti-MUC1 IgG levels. | (27) |