Table 1 Phenotypes and immunosuppressive feature of MDSCs in hematological malignancies
Diseases | MDSCs type | Phenotype | Immunosuppressive features | Clinical significance | Year/reference |
|---|---|---|---|---|---|
DLBCL | ↑M-MDSCs | CD45+CD11b+CD33+HLA-DRlow/−CD14+CD15− | / | Blood concentration of MDSCs and Treg cells may be good prognostic markers for overall survival after 2 years in R/R DLBCL. | 2021 [59] |
↑PMN-MDSCs | CD45+CD11b+CD33+HLA-DRlow/−CD14−CD15+ | ||||
DLBCL | ↑M-MDSCs | CD14+HLA-DR− | ↑IL-10, S100A12, PD-L1 | Only M-MDSCs number was correlated with the International Prognostic Index, event-free survival, and number of circulating Tregs. | 2016 [55] |
↑PMN-MDSCs | Lin−CD123−HLA-DR−CD33+CD11b+ | ||||
DLBCL | ↑M-MDSCs | CD14+HLA-DR−/low | ↑IL-35 | Increased levels of M-MDSCs are positively associated with tumor progression and inversely correlated with OS. The level of M-MDSCs can be defined as a biomarker for a poor prognosis in DLBCL patients. | 2021 [58] |
B-NHL | ↑M-MDSCs | CD14+ CD33+ HLA-DR− /low | Treg cell | MDSCs expansion was closely associated with disease progression (tumor stage, LDH levels and B syndromes). | 2022 [51] |
↑PMN-MDSCs | CD10−HLA-DR− /low | ||||
HL, NHL | ↑PMN-MDSCs | CD66b+CD33dimHLA-DR− | / | Higher frequencies of PMN-MDSCs correlated significantly with unfavorable prognostic index scores and a shorter freedom from disease progression. | 2016 [60] |
AML | ↑M-MDSCs | CD14+HLA-DRlow/− M-MDSC | / | Elevated circulating M-MDSCs in patients with AML were significantly associated with low complete remission (CR) rate, high relapse/refractory rate, and poor long-term survival. | 2020 [172] |
AML | ↑MDSCs | CD11b+HLA-DR−CD33+Lin− | ↑IL-10; ↓IFN-γ; MUC1 signaling | MDSCs are expanded in patients with AML and contribute to tumor-related immune suppression. | 2017 [91] |
AML | ↑MDSCs | CD11b+ CD33+ HLA-DR− | ↑VISTA | VISTA is highly expressed on MDSCs and knockdown of VISTA significantly diminished the MDSCs-mediated inhibition of T cell proliferation. | 2018 [93] |
AML | ↑MDSC-like blast | CD11b+CD33+HLA-DR− | ↑iNOS, ARG1 | Patients with high MDSC-like blasts at diagnosis showed substantially shorter overall survival and leukemia-free survival relative to low MDSC-like blasts patients. | 2020 [173] |
AML | ↑M-MDSCs | CD14+CD33+IDO+HLA-DRlow | ↑IDO | AMG 330 may achieve anti-leukemic efficacy not only through T-cell-mediated cytotoxicity against AML-blasts but also against CD33 + MDSCs. MDSCs levels could represent a biomarker for the patients’ clinical responsiveness towards an AMG 330-based therapy. | 2018 [174] |
AML | ↑M-MDSCs | CD14+HLA-DRlow | ↑IDO, S100A8/9, cEBPβ | Targeting protein palmitoylation in AML could interfere with the leukemogenic potential and block MDSCs accumulation to improve immunity. | 2020 [92] |
ALL | ↑MDSCs | Lin−HLA-DR−CD33+CD11b+ | / | The correlation between the frequencies of the two immunosuppressive populations, MDSCs and Treg cell in pediatric patients with B-ALL as compared to healthy volunteers. | 2018 [175] |
B-ALL | ↑PMN-MDSCs | CD45+CD19−HLA-DR−CD11b+CD33+CD15+ | ↑DCs, Direct cell-cell contact, STAT3 | PMN-MDSCs levels correlated positively with clinical therapeutic responses and B-ALL disease prognostic markers, including minimal residual disease, and the frequencies of CD20 + and blast cells. | 2017 [76] |
↑M-MDSCs | CD45+CD19−HLA-DR−CD11b+CD33+CD14+ | ||||
APL | ↑M-MDSCs | CD33+CD14+HLA-DR− | ↑ARG1, iNOS; IL-13 blocking | Tumour-activated ILC2s secrete IL-13 to induce myeloid-derived suppressor cells and support tumour growth. | 2017 [137] |
CML | ↑PMN-MDSCs | CD11b+CD33+CD14−HLADR− | ↑ARG1 | PMN-MDSCs and M-MDSCs were significantly higher at diagnosis compared to HD and decreased to normal levels after IM therapy. T-reg resulted significantly increased in respect to HD and they directly correlated with PMN-MDSCs. | 2014 [88] |
CML | ↑MDSCs | CD11b+CD14−CD33+ | ↑ARG1 | T cells in CML patients may be under the control of different immune escape mechanisms (MDSCs, Arg1, PD-L1/PD-1 and sCD25) that could hamper the use of immunotherapy in these patients. | 2013 [89] |
CML | ↑PMN-MDSCs | CD11b+CD33+CD15+CD14−HLA-DR− | ↑ARG1, TNFα, IL1β, COX2, IL6 | G-MDSCs isolated from CML patients were not able to inhibit T lymphocyte proliferation. MDSCs differentiated in presence of transformed MSC, exhibited an enhanced inhibitory effect on T cell proliferation. | 2016 [176] |
CLL | ↑M-MDSCs | CD14+CD11b+CD15−HLA-DR−/low | ↑IL-10, TGF-β1 | The level of IL-10 and TGF-b1 expression in circulating M-MDSCs in correlation with clinical and laboratory parameters characterizing disease activity and patients’ immune status (Rai stages, ZAP-70-positive, CD38-positive, genetic aberrations). | 2020 [83] |
CLL | ↑M-MDSCs | CD14+CD11b+CD15−HLA-DR−/low | ↑IDO, IL-10, TGF-Β1 | CLL patients with M-MDSCs percentages above 9.35% (according to the receiver operating characteristic (ROC) analysis) had a shorter time-to-treatment and shorter survival time than the group with a lower percentage of M-MDSCs. The M-MDSCs percentage was higher in patients with adverse prognostic factors (i.e., 17p and 11q deletion and CD38 and ZAP-70 expression). | 2020 [177] |
CLL | ↑PMN-MDSCs | HLA-DRlowCD11b+CD33+CD15+ | ↑CD124, CD80, PD-L1/2 | The balance between the number of PMN-MDSCs and M-MDSCs affects the function of CLL course (high-risk cytogenetics (11q − and 17p−), ZAP70 levels). | 2021 [84] |
↑M-MDSCs | HLA-DRlowCD11b+CD33+CD14+ | ↑TGFβ membrane protein | |||
MM | ↑PMN-MDSCs | CD11b+CD13+CD16+ | ↑Inflammatory cytokines | A set of optimal markers (CD11b + CD13 + CD16+) was found, which can accurately detect PMN-MDSCs in MM. | 2020 [103] |
MM | ↑PMN-MDSCs | CD11b+CD15+CD14−HLADR− | ↑ARG1, TNFα, PROK2 | Mesenchymal stem cells support MM cell growth and survival by promoting MDSCs activation. | 2016 [97] |
MM | ↑PMN-MDSCs | HLA-DR−/lowCD33+CD11b+CD15+CD14− | ↑CSCs core genes, piRNA-823 | There was a correlation between the frequency of PMN-MDSCs and overall survival rate of MM patients. | 2019 [101] |
MDS | ↑MDSCs | CD33+Lin−HLA-DR− | ↑TIM3, CEACAM1, IL-1β, IL-18 | Suppressed immune function of CD8 + T cells after co-culture of either MDSC or rhCEACAM1 with CD8 + T cells. | 2022 [112] |
MDS | ↑PMN-MDSCs | Lin−CD11b+CD33+CD15+ | ↑CXCR4, CX3CR1 | The expansion of MDSCs in MDS correlates with increased risk of disease progression toward AML and also positively correlates with Treg numbers in high risk MDS. | 2015 [108] |
MDS | ↑MDSCs | Lin−HLA-DR−CD33+ | ↑IL-10, TGF-β | MDSCs in higher-risk MDS have a stronger immunosuppressive effect and might be related to poor prognosis. | 2020 [109] |
MDS | ↑MDSCs | Lin-HLA-DR-CD33+ | ↑STAT3, ARG1 | MDSCs, which are more pervasive in MDS especially in the high-risk patients, can be STAT3-overactivated and facilitate immune escape and disease progression. | 2021 [110] |
MDS | ↑MDSCs | PD-L1+CD33+CD14+ | ↑PD-L1 | Abnormal expansion and activation of MDSC lead to ineffective hematopoiesis. | 2019 [113] |
allo-HSCT | ↑e-MDSCs | HLA-DR−/lowCD33+CD16− | ↑TGF-β | e-MDSCs prevented acute GVHD in a humanized mouse model in vivo. | 2019 [178] |
haplo-HSCT | ↑PMN-MDSCs | CD45+Lin−HLA-DR−/lowCD33+CD11b+CD14−CD66b+ | ↑Soluble factors, IDO, PEG2; Exosomes | PMN-MDSCss contained in the graft exerts an early inhibitory effect on NK cell-mediated GVL activity. | 2020 [179] |
allo-HSCT | ↑M-MDSCs | CD14+HLA-DR−/lowCD80+CD86−CD40−CD64−CD16−CD163+ | ↑IL-6, TNF‐α | Accumulation of MDSCs in the graft and in peripheral blood result in the successful control of severe aGVHD and long-term survival without influence on risk of recurrence after allo‐HSCT. | 2016 [180] |