Table 1.
Summary of MDSC representative phenotype and their prognostic role in different hematological cancers.
| Diseases | Source | MDSC subgroups/phenotype definition | Clinical finding | Ref | |
|---|---|---|---|---|---|
| Leukemia | AML | PB BM |
M-MDSC: CD11b+HLA-DR-CD14-/+CD33+CD15-
G-MDSC: CD11b+HLA-DR-CD14-CD33+CD15+ |
Higher MDSC level in PB and BM of AML patients VS. HD. | (21) |
| PB | M-MDSC: CD14+HLA-DRlow/- | Higher circulating M-MDSC frequencies in CD14+ monocytes and PBMC VS. HD (p < 0.01). | (22) | ||
| PB | eMDSC: Lin-(CD3/14/15/19/56)HLA-DR-CD33+ | Unknown | (23) | ||
| BM | MDSC: CD33+CD11b+HLA-DRlow/neg | Significantly increased MDSC in BM (p < 0.01). | (24) | ||
| CML | PB | M-MDSC: CD14+HLA-DR-
G-MDSC: CD11b+CD33+CD14-HLA-DR- |
MDSC levels were increased at diagnosis and returned to normal levels after therapy (p < 0.001, p < 0.0001). |
(25) | |
| PB | MDSC: CD11b+ CD14-CD33+ | PB MDSC levels were increased in samples from Sokal high-risk patients (p < 0.05). | (26) | ||
| B-ALL | PB BM |
M-MDSC: CD45+CD19-HLA- DR-CD11b+CD33+CD14+
G-MDSC: CD45+CD19-HLA- DR-CD11b+CD33+CD15+ |
G-MDSC were significantly elevated in PB and BM vs. age-matched HD (p < 0.05, p < 0.01). G-MDSC levels correlated positively with clinical therapeutic responses and B-ALL disease prognostic markers. |
(27) | |
| PB | MDSC: LinHLA-DR-CD33+CD11b+ | MDSC levels significantly increased in early diagnosed B-ALL patients VS. HD. | (28) | ||
| CLL | PB | M-MDSC: CD14+HLA-DRlow/- | The M-MDSC were upregulated in patients (p < 0.0001) and were correlated with CLL tumor progression, poor prognosis, and correlated with the presence of CD4+ T and CD5+CD19+ cells. | (29) | |
| PB | M-MDSC: CD14+CD11b+CD15-HLA-DRlow/- | M-MDSC were increased in PB of CLL Patients and correlated with The Rai Stage (p < 0.001), and a close association with unfavorable prognostic markers. | (30) | ||
| PB | M-MDSC: CD14+CD11b+CD15-HLA-DRlow/- | Higher median percentage of M-MDSC with IL-10 or TGF-1 expression in CLL patients than in HD (p < 0.001, p < 0.0001). | (31) | ||
| PB | M-MDSC: HLA-DR CD11b+CD33+CD14+
G-MDSC: HLA-DRlowCD11b+CD33+CD15+ |
Higher numbers of G-MDSC in patients correlated with different Th- subsets, and were more strongly associated with a poor clinical course than M-MDSC. | (32) | ||
| Lymphoma | DLBCL | PB | M-MDSC: CD14+HLA-DR- G-MDSC: Lin-CD123-HLA-DR-CD33+CD11b+ | Increased M-MDSC and G-MDSC populations in whole blood VS. HD (p = 0.001, p = 0.01). M-MDSC were correlated with the IPI and EFS (p = 0.034, hazard ratio = 0.19). | (33) |
| PB | M-MDSC: CD14+HLA-DRlow/- | Increased frequency of M-MDSC was found in ND vs. HD (p < 0.01) and associated with tumor progression in patients. (ND vs. Rel VS. Rem, p < 0.05, p < 0.01). | (34) | ||
| HL | PB | MDSC: CD11b+CD33+CD14-CD34+HLA-DR- M-MDSC: CD14+HLA-DRlow/-
G-MDSC: CD11b+CD33+CD14-HLA-DR-Lin- |
All MDSC subsets (immature MDSC, G-MDSC, M-MDSC) were higher in patients VS. HD (p = 0.03, p = 0.02, p 0.04), and higher MDSC percentages were present in non-responders. CD34+ immature MDSC were predictive for a short PFS in HL patients (p = 0.03). | (35) | |
| B-NHL | BM | M-MDSC: CD14+CD33+HLA-DR-
G-MDSC: CD10-HLA-DRlow/- |
Differences in M-MDSC (ND, Rem and Rel of B-NHL patients vs. HD, p < 0.0001, P < 0.001, p < 0.001). G-MDSC% was increased in PB (ND and Rem and Rel of B-NHL patients vs. HD, p <0.0001, p < 0.0001, p < 0.0001). | (36) | |
| Multiple Myeloma | PB | M-MDSC: CD14+HLA-DRlow/- | Increased level of MDSC in patients with MM at diagnosis VS. HD (p < 0.05). | (37) | |
| PB BM |
M-MDSC: CD14+HLA-DRlow/- | M-MDSC of ND MM patients were increased in PB and BM vs. HD (p < 0.01), and were associated with MM progression and response to therapy (ND and Rem and Rel of MM patients VS. HD, p < 0.01). | (38) | ||
| PB BM |
M-MDSC: CD11b+CD14+HLA-DRlow/-
G-MDSC: CD11b+CD33+HLA-DRlow/-CD14- CD15+ |
PB M-MDSC show correlation with serum creatinine, lactate dehydrogenase, and β-microglobulin and inverse correlation with hemoglobin level PB M-MDSC of patients with progressive disease showed higher levels than those of patients at diagnosis and in complete response (p = 0.003 and 0.026, respectively). BM M-MDSC levels were higher in patients with progressive disease than those in patients at diagnosis (p = 0.007). PB M-MDSC > 0.3%) at diagnosis had an independent adverse prognostic impact on OS. |
(39) | ||
| PB | M-MDSC: CD14+HLA-DRlow/-
eMDSC: CD11b+Lin-(CD3/14/15/19/56)HLA- DR-CD33+ |
In the pre-ASCT analyses, lower M-MDSC (median) were associated with a longer time to progression (TTP) (p < 0.001). Pre-ASCT M-MDSC more strongly inhibited the in vitro cytotoxic effect of mephalan compared with pre-ASCT eMDSC (p < 0.01). | (40) | ||
| PB | M-MDSC: G-MDSC: CD10-HLA-DRlow/- | Higher G-MDSC in PB of ND and Rel VS. HD (p = 0.03, p < 0.001). | (41) | ||
| PB BM |
M-MDSC: CD11b+CD33+CD15-
G-MDSC: CD11b+CD33+HLA-DRlow/-CD14- CD15+ |
G-MDSC are increased in BMMC of MM patients (highest in RRMM) VS. MGUS/SMM patients or HD (p < 0.05). G-MDSC in BMMC and PBMC of MM patients expressed higher levels of PD-L1 (p < 0.05). | (42) | ||
| PB BM |
G-MDSC: HLA-DRlow/-CD33+CD11b+CD15+CD14 | There is an association between high G-MDSC levels and poor OS in PB and BM of MM patients vs. HD (p < 0.05, p < 0.01). | (43) | ||
| PB | M-MDSC: CD33+CD11b+HLA-DRlow/-CD14+CD15 G-MDSC: CD33+CD11b+HLA-DRlow/-CD14- CD15+ |
The G-MDSC subpopulation was increased in samples from patients with MM (both patients with progressive disease and patients with stable disease vs. age-matched controls, p < 0.0001, p < 0.0445.) | (44) | ||
| PB | M-MDSC: CD66b+CD15-CD14+HLA-DR-
G-MDSC: CD66b+CD15+CD14-HLA-DR- |
G-MDSC and M-MDSC were increased in PB of MM VS. HD (p < 0.0001). Argl+G-MDSC percentage was increased in PB of ND MM patients VS. MGUS (p < 0.0001), and it was higher in RRMM VS. ND (p < 0.0001). | (45) | ||
| BM | G-MDSC: CD11b+CD13+CD16+ | G-MDSCs are defined as CD11b+CD13+CD16+ neutrophils in MM. | (46) |
PB, peripheral blood; BM, bone marrow; HD, health donors; AML, acute myeloid leukemia; CML, chronic myeloid leukemia; B-ALL, B-Cell acute lymphoblastic leukemia; CLL, chronic lymphocytic leukemia; DLBCL, diffuse large B cell lymphoma; HL, Hodgkin’s lymphoma; B-NHL, B-Cell non-Hodgkin lymphoma; M-MDSC, monocytic myeloid derived suppressor cells; G-MDSC, granulocytic myeloid derived suppressor cells; IL-10, interleukin 10; TGF-β1, transforming growth factor beta 1; Th cells, helper T-cells; ND, newly diagnosed; Rel, relapsed; Rem, remission; IPI, international prognostic index; EFS, event-free survival; PFS, progression-free survival; BMMC, bone marrow mononuclear cell; PBMC, peripheral blood mononuclear cell; RRMM, relapsed/refractory multiple myeloma; OS, Overall survival; MGUS, monoclonal gammopathy of undetermined significance.