Myeloid derived suppressor cells (MDSC) are CD11b
+Gr1
+ immunosuppressive, incompletely differentiated myeloid progenitor cells originally identified in tumor bearing mice [
19]. MDSC accumulate in the blood, spleen, lymph nodes, bone marrow and tumors of tumor-bearing animals and patients [
20‐
24]. MDSCs inhibit innate and adaptive immunity, promoting tumor immune escape. MDSC are a heterogeneous population of cells that lack the expression of cell surface markers that are specifically expressed on macrophages or DC [
25]. In mice, MDSC are uniformly characterized by the expression of Gr1 and CD11b. Gr1 includes the macrophage and neutrophil markers Ly6C and Ly6G, respectively, whereas CD11b (also known as integrin αM) is characteristic for the myeloid- cell linage. In recent years, several other surface molecules have been used to identify additional subset of immunosuppressive MDSC, including CD80 [
26], CD115 (also known as macrophage colony stimulating factor (M-CSF) receptor) and CD124 (IL-4 receptor alpha chain, IL-4Rα) [
27]. In addition, nuclear morphology has also been used to characterize mouse MDSC. Mononuclear CDllb
+Gr1
midLy6G
+/−Ly6C
highCD49d
+ cells are considered “monocytic” whereas polymorphonuclear CDllb
+Gr1
highLy6G
+Ly6C
negCD49d
neg MDSC are considered granulocytic [
28‐
30]. Subpopulations of MDSC can give rise to CD11b
+Gr1
lowF4/80
+MHCII
+ macrophages with potent immunosuppressive properties, underscoring the potential biological continuum of immature myeloid cells, monocytes, and macrophages [
20,
25,
31].
In patients with glioblastoma, breast cancer, colon cancer, lung cancer or kidney cancer, MDSC have been defined as Lin
negCDllb
+HLA-DR
negCD33
+ cells that express the common myeloid marker CD33 but lack mature monocyte and lymphoid cell linage markers (Lin
neg = CD14
neg, CD3
neg, CD19
neg) and lack the MHC class II molecule HLA-DR [
32]. In patients with renal cancer, polymorphonuelcar MDSC have been shown to express CD11b
+ CD14
negCD15
+CD66b
+ VEGFR1
+[
33] whereas in patients with melanoma, prostate cancer, hepatocellular carcinoma or head and neck cancer, immunosuppressive monocytic CD11b
+ CD14
+ HLA-DR
low/neg MDSC were found [
21,
34‐
36]. These cells are associated with increased tumor burden and poor prognosis in patients with breast and colorectal cancer [
24,
37].