J. E. Talmadge and D. I. Gabrilovich, History of myeloid derived suppressor cells (MDSCs) in the macro-and micro-environment of tumourbearing hosts, Nat Rev Cancer, vol.13, pp.739-752, 2013.

D. I. Gabrilovich, V. Bronte, and S. H. Chen, The terminology issue for myeloid-derived suppressor cells, Cancer Res, vol.67, pp.425-1425, 2007.

D. I. Gabrilovich, Myeloid-derived suppressor cells, Cancer Immunol Res, vol.5, pp.3-8, 2017.

F. Veglia, M. Perego, and D. Gabrilovich, Myeloid-derived suppressor cells coming of age, Nat Immunol, vol.19, pp.108-119, 2018.

V. Bronte, S. Brandau, and S. H. Chen, Recommendations for myeloidderived suppressor cell nomenclature and characterization standards, Nat Commun, vol.7, pp.1-10, 2016.

T. Condamine, G. A. Dominguez, and J. I. Youn, Lectin-type oxidized LDL receptor-1 distinguishes population of human polymorphonuclear myeloid-derived suppressor cells in cancer patients, Sci Immunol, vol.1, p.8943, 2016.

V. Umansky, G. J. Adema, and J. Baran, Interactions among myeloid regulatory cells in cancer, Cancer Immunol Immunother, 2018.

C. R. Millrud, C. Bergenfelz, and K. Leandersson, On the origin of myeloidderived suppressor cells, Oncotarget, vol.8, pp.3649-3665, 2017.

Y. Zhao, T. Wu, and S. Shao, Phenotype, development, and biological function of myeloid-derived suppressor cells, Oncoimmunology, vol.5, p.1004983, 2016.

K. De-veirman, V. Valckenborgh, E. Lahmar, and Q. , Myeloid-derived suppressor cells as therapeutic target in hematological malignancies, Front Oncol, vol.4, pp.1-11, 2014.

I. H. Younos, F. Abe, and J. E. Talmadge, Myeloid-derived suppressor cells: their role in the pathophysiology of hematologic malignancies and potential as therapeutic targets, Leuk Lymphoma, vol.56, pp.2251-2263, 2015.

I. L. Vladimirovna, E. Sosunova, and A. Nikolaev, Mesenchymal stem cells and myeloid derived suppressor cells: common traits in immune regulation, J Immunol Res, p.7121580, 2016.

, The immunosuppressive potential of the cells should preferentially be performed by a functional assay demonstrating their T-cell suppressive capacity. If the candidate MDSC population lacks a T-cell suppressive function, then this potential should indirectly be demonstrated by the biochemical and/or molecular characterization of the cells. The figure depicts representative functional assays and biochemical and molecular characteristics of MDSCs according to recent recommendations. 5 ARG1 = arginase-1, BM = bone marrow, BMMCs = bone marrow mononuclear cells, C/EBPb = CCAAT/enhancer binding protein b, CHOP = C/EBP homologous protein, ELISA = enzyme-linked immunosorbent assay, ELISPOT = enzyme-linked immunospot, e-MDSCs = early MDSCs, IFNg = interferon g, IL= interleukin, IRF8 = interferon regulatory factor 8, MDSC = myeloid-derived suppressor cells, M-MDSCs = monocytic MDSCs, NOS = nitric oxide synthases, NOX NADPH = oxidase, PB = peripheral blood, PBMCs = peripheral blood mononuclear cells, PD-L1 = programmed death-ligand 1, PGE2 = prostaglandin E2, PHA = phytohemagglutinin, PMN-MDSCs = polymorphonuclear MDSCs, PNT = peroxynitrite, RB = retinoblastoma, RNS = reactive nitrogen species, ROR = RAR-related orphan receptors, ROS = reactive oxygen species, STAT = signal transducer and activator of transcription, Algorithm for the characterization of MDSCs in human PB samples or BM aspirates. For the characterization of a candidate cell population as MDSCs, both the specific immunophenotypic characteristics and the immunosuppressive potential of the cells should be determined

T. Barbui, J. Thiele, and H. Gisslinger, The 2016 WHO classification and diagnostic criteria for myeloproliferative neoplasms: document summary and in-depth discussion, Blood Cancer J, vol.8, p.15, 2018.

L. Christiansson, S. Söderlund, and E. Svensson, Increased level of myeloid-derived suppressor cells, programmed death receptor ligand 1/programmed death receptor 1, and soluble CD25 in Sokal high risk chronic myeloid leukemia, PLoS ONE, vol.8, pp.1-12, 2013.

C. Giallongo, N. Parrinello, and D. Tibullo, Myeloid derived suppressor cells (MDSCs) are increased and exert immunosuppressive activity together with Polymorphonuclear Leukocytes (PMNs) in chronic myeloid leukemia patients, PLoS ONE, vol.9, pp.1-13, 2014.

C. Giallongo, N. L. Parrinello, L. Cava, and P. , Monocytic myeloidderived suppressor cells as prognostic factor in chronic myeloid leukaemia patients treated with dasatinib, J Cell Mol Med, vol.22, pp.1070-1080, 2018.

A. Hughes, J. Clarson, and C. Tang, CML patients with deep molecular responses to TKI have restored immune effectors and decreased PD-1 and immune suppressors, Blood, vol.129, pp.1166-1176, 2017.

C. Giallongo, A. Romano, and N. L. Parrinello, Mesenchymal stem cells (MSC) regulate activation of granulocyte-like myeloid derived suppressor cells (G-MDSC) in chronic myeloid leukemia patients, PLoS ONE, vol.11, pp.1-13, 2016.

G. Barosi, An immune dysregulation in MPN, Curr Hematol Malig Rep, vol.9, pp.331-339, 2014.

J. C. Wang, A. Kundra, and M. Andrei, Myeloid-derived suppressor cells in patients with myeloproliferative neoplasm, Leuk Res, vol.43, pp.39-43, 2016.

H. Sun, Y. Li, and Z. Zhang, Increase in myeloid-derived suppressor cells (MDSCs) associated with minimal residual disease (MRD) detection in adult acute myeloid leukemia, Int J Hematol, vol.102, pp.579-586, 2015.

A. R. Pyzer, D. Stroopinsky, and H. Rajabi, MUC1-mediated induction of myeloid-derived suppressor cells in patients with acute myeloid leukemia, Blood, vol.129, pp.1791-1802, 2017.

Y. Liu, Y. Chen, and Y. He, Expansion and activation of granulocytic, myeloid-derived suppressor cells in childhood precursor B cell acute lymphoblastic leukemia, J Leukoc Biol, vol.102, pp.449-458, 2017.

M. L. Salem, M. R. El-shanshory, and S. H. Abdou, Chemotherapy alters the increased numbers of myeloid-derived suppressor and regulatory T cells in children with acute lymphoblastic leukemia, Immunopharmacol Immunotoxicol, vol.40, pp.158-167, 2018.

D. A. Arber, A. Orazi, and R. Hasserjian, The 2016 revision to the World Health Organization classi fi cation of myeloid neoplasms and acute leukemia, Blood, vol.127, pp.2391-2406, 2016.

S. Y. Kordasti, B. Afzali, and Z. Lim, IL-17-producing CD4+ T cells, proinflammatory cytokines and apoptosis are increased in low risk myelodysplastic syndrome, Br J Haematol, vol.145, pp.64-72, 2009.

D. I. Gabrilovich and S. Nagaraj, Myeloid-derived suppressor cells as regulators of the immune system, Nat Rev Immunol, vol.9, pp.162-174, 2009.

X. Chen, E. A. Eksioglu, and J. Zhou, Induction of myelodysplasia by myeloid-derived suppressor cells, J Clin Invest, vol.123, pp.4595-4611, 2013.

F. Zhao, B. Hoechst, and A. Duffy, S100A9 a new marker for monocytic human myeloid-derived suppressor cells, Immunology, vol.136, pp.176-183, 2012.

Y. Sato, Y. Goto, and N. Narita, Cancer cells expressing toll-like receptors and the tumor microenvironment, Cancer Microenviron, vol.2, pp.205-214, 2009.

A. O. Kittang, S. Kordasti, and K. E. Sand, Expansion of myeloid derived suppressor cells correlates with number of T regulatory cells and disease progression in myelodysplastic syndrome, Oncoimmunology, vol.5, pp.1-9, 2016.

Y. Mei, B. Zhao, and A. A. Basiorka, Age-related inflammatory bone marrow microenvironment induces ineffective erythropoiesis mimicking del(5q), MDS. Leukemia, vol.32, pp.1023-1033, 2018.

P. Sinha, C. Okoro, and D. Foell, Proinflammatory S100 proteins regulate the accumulation of myeloid-derived suppressor cells, J Immunol, vol.181, pp.4666-4675, 2008.

K. Sand, J. Theorell, and Ø. Bruserud, Reduced potency of cytotoxic T lymphocytes from patients with high-risk myelodysplastic syndromes, Cancer Immunol Immunother, vol.65, pp.1135-1147, 2016.

H. J. Bontkes, J. M. Ruben, and C. Alhan, Azacitidine differentially affects CD4 pos T-cell polarization in vitro and in vivo in high risk myelodysplastic syndromes, Leuk Res, vol.36, pp.921-930, 2012.

E. A. Eksioglu, X. Chen, and K. H. Heider, Novel therapeutic approach to improve hematopoiesis in low risk MDS by targeting MDSCs with the Fc-engineered CD33 antibody B, Leukemia, vol.31, pp.2172-2180, 2017.

K. Movahedi, M. Guilliams, and J. Bossche, Identification of discrete tumor-induced myeloid-derived suppressor cell subpopulations with distinct T cell-suppressive activity, Blood, vol.111, pp.4233-4244, 2012.

J. Youn, S. Nagaraj, and M. Collazo, Subsets of myeloid-derived suppressor cells in tumor-bearing mice, J Immunol, vol.181, pp.5791-5802, 2008.

P. Serafini, S. Mgebroff, and K. Noonan, Myeloid-derived suppressor cells promote cross-tolerance in B-cell lymphoma by expanding regulatory T cells, Cancer Res, vol.68, pp.5439-5449, 2008.

O. Marini, C. Spina, and E. Mimiola, Identification of granulocytic myeloid-derived suppressor cells (G-MDSCs) in the peripheral blood of Hodgkin and non-Hodgkin lymphoma patients, Oncotarget, vol.7, pp.27676-27688, 2016.

I. Azzaoui, F. Uhel, and D. Rossille, T-cell defect in diffuse large B-cell lymphomas involves expansion of myeloid derived suppressor cells expressing IL-10, PD-L1 and S100A12, Blood, vol.128, pp.1081-1092, 2016.
URL : https://hal.archives-ouvertes.fr/hal-01394657

Y. Lin, M. P. Gustafson, and P. A. Bulur, Immunosuppressive CD14 + HLA-DR low/À monocytes in B-cell non-Hodgkin lymphoma, Blood, vol.117, pp.872-881, 2011.

M. P. Gustafson, R. S. Abraham, and Y. Lin, Association of an increased frequency of CD14+ HLA-DR lo/neg monocytes with decreased time to progression in chronic lymphocytic leukaemia (CLL), Br J Haematol, vol.156, pp.674-676, 2012.

R. Jitschin, M. Braun, and M. Büttner, CLL-cells induce IDOhi CD14+ HLA-DRlo myeloid derived suppressor cells that inhibit T-cell responses and promote TRegs, Blood, vol.124, pp.750-760, 2014.

A. Romano, N. L. Parrinello, and C. Vetro, Circulating myeloid-derived suppressor cells correlate with clinical outcome in Hodgkin Lymphoma patients treated up-front with a risk-adapted strategy

, Br J Haematol, vol.168, pp.689-700, 2015.

A. Betsch, O. Rutgeerts, and S. Fevery, Myeloid-derived suppressor cells in lymphoma: the good, the bad and the ugly, Blood Rev, vol.32, pp.490-498, 2018.

M. P. Gustafson, Y. Lin, and M. L. Maas, A method for identification and analysis of non-overlapping myeloid immunophenotypes in humans, PLoS ONE, vol.10, pp.1-19, 2015.

T. Tadmor, R. Fell, and A. Polliack, Absolute monocytosis at diagnosis correlates with survival in diffuse large B-cell lymphomapossible link with monocytic myeloid-derived suppressor cells

, Hematol Oncol, vol.31, pp.325-331, 2013.

C. Wu, X. Wu, and X. Liu, Prognostic significance of monocytes and monocytic myeloid-derived suppressor cells in diffuse large B-cell lymphoma treated with R-CHOP, Cell Physiol Biochem, vol.39, pp.521-530, 2016.

L. J. Geskin, O. E. Akilov, and S. Kwon, Therapeutic reduction of cellmediated immunosuppression in mycosis fungoides and Sézary syndrome, Cancer Immunol Immunother, vol.67, pp.423-434, 2018.

M. S. Raab, K. Podar, and I. Breitkreutz, Multiple myeloma, Lancet, vol.374, pp.324-339, 2009.
URL : https://hal.archives-ouvertes.fr/inserm-00130206

C. Botta, A. Gullã, and P. Correale, Myeloid-derived suppressor cells in multiple myeloma: pre-clinical research and translational opportunities, Front Oncol, vol.4, pp.1-12, 2014.

Y. Yazdani, M. Mohammadnia-afrouzi, and M. Yousefi, Myeloidderived suppressor cells in B cell malignancies, Tumor Biol, vol.36, pp.7339-7353, 2015.

E. Malek, M. De-lima, and J. J. Letterio, Myeloid-derived suppressor cells: the green light for myeloma immune escape, Blood Rev, vol.30, pp.341-348, 2016.

K. De-veirman, V. Ginderachter, J. A. Lub, and S. , Multiple myeloma induces Mcl-1 expression and survival of myeloid-derived suppressor cells, Oncotarget, vol.6, pp.10532-10547, 2015.

E. Van-valckenborgh, E. Schouppe, and K. Movahedi, Multiple myeloma induces the immunosuppressive capacity of distinct myeloid-derived suppressor cell subpopulations in the bone marrow, Leukemia, vol.26, pp.2424-2428, 2012.

I. R. Ramachandran, T. Condamine, and C. Lin, Bone marrow PMN-MDSCs and neutrophils are functionally similar in protection of multiple myeloma from chemotherapy, Cancer Lett, vol.371, pp.117-124, 2016.

J. Wang, D. Veirman, K. Faict, and S. , Multiple myeloma exosomes establish a favourable bone marrow microenvironment with enhanced angiogenesis and immunosuppression, J Pathol, vol.239, pp.162-173, 2016.

M. Binsfeld, J. Muller, and V. Lamour, Granulocytic myeloid-derived suppressor cells angiogenesis in the context of multiple myeloma

, Oncotarget, vol.7, pp.37931-37943, 2016.

J. Wang, D. Veirman, K. , D. Beule, and N. , The bone marrow microenvironment enhances multiple myeloma progression by exosome-mediated activation of myeloid-derived suppressor cells, Oncotarget, vol.6, pp.43992-44004, 2015.

Y. Xu, X. Zhang, and H. Liu, Mesenchymal stromal cells enhance the suppressive effects of myeloid-derived suppressor cells of multiple myeloma, Leuk Lymphoma, vol.58, pp.2668-2676, 2017.

J. Zhuang, J. Zhang, and S. T. Lwin, Osteoclasts in multiple myeloma are derived from Gr-1+CD11b+ myeloid-derived suppressor cells, PLoS ONE, vol.7, p.48871, 2012.

I. Ramachandran, A. Martner, and A. Pisklakova, Myeloid derived suppressor cells regulate growth of multiple myeloma by inhibiting T cells in bone marrow, J Immunol, vol.190, pp.3815-3823, 2013.

P. Serafini, K. Meckel, and M. Kelso, Phosphodiesterase-5 inhibition augments endogenous antitumor immunity by reducing myeloidderived suppressor cell function, J Exp Med, vol.203, pp.2691-2702, 2006.

C. Giallongo, D. Tibullo, and N. L. Parrinello, Granulocyte-like myeloid derived suppressor cells (G-MDSC) are increased in multiple myeloma and are driven by dysfunctional mesenchymal stem cells (MSC), Oncotarget, vol.7, pp.85764-85775, 2016.

G. T. Görgun, G. Whitehill, and J. L. Anderson, Tumor-promoting immune-suppressive myeloid-derived suppressor cells in the multiple myeloma microenvironment in humans, Blood, vol.121, pp.2975-2987, 2013.

J. Favaloro, T. Liyadipitiya, and R. Brown, Myeloid derived suppressor cells are numerically, functionally and phenotypically different in patients with multiple myeloma, Leuk Lymphoma, vol.55, pp.2893-2900, 2014.

Z. Wang, L. Zhang, and H. Wang, Tumor-induced CD14+HLA-DRÀ/ low myeloid-derived suppressor cells correlate with tumor progression and outcome of therapy in multiple myeloma patients, Cancer Immunol Immunother, vol.64, pp.389-399, 2015.

S. Karpatkin, Autoimmune (idiopathic) thrombocytopenic purpura, Lancet, vol.349, pp.1531-1536, 1997.

Y. Hou, Q. Feng, and M. Xu, High-dose dexamethasone corrects impaired myeloid-derived suppressor cell function via Ets1 in immune thrombocytopenia, Blood, vol.127, pp.1587-1597, 2016.

J. Zhou, Y. Zhou, and J. Wen, Circulating myeloid-derived suppressor cells predict disease activity and treatment response in patients with immune thrombocytopenia, Brazilian J Med Biol Res, vol.50, pp.2-7, 2017.

X. Shao, B. Wu, and L. Cheng, Distinct alterations of CD68+CD163+ M2-like macrophages and myeloid-derived suppressor cells in newly diagnosed primary immune thrombocytopenia with or without CR after high-dose dexamethasone treatment, J Transl Med, vol.16, pp.1-11, 2018.

R. Aslam, W. R. Burack, and G. B. Segel, Intravenous immunoglobulin treatment of spleen cells from patients with immune thrombocytopenia significantly increases the percentage of myeloid-derived suppressor cells, Br J Haematol, vol.181, pp.262-264, 2018.

H. A. Papadaki, K. Stamatopoulos, and A. Damianaki, Activated Tlymphocytes with myelosuppressive properties in patients with chronic idiopathic neutropenia, Br J Haematol, vol.128, pp.863-876, 2005.

N. Bizymi, M. Velegraki, and A. Damianaki, Low proportion of myeloid derived suppressor cell populations in the peripheral blood of patients with chronic idiopathic neutropenia, HemaSphere, vol.2, issue.1, pp.103-104, 2018.

J. Xin, P. Breslin, and W. Wei, Necroptosis in spontaneously-mutated hematopoietic cells induces autoimmune bone marrow failure in mice, Haematologica, vol.102, pp.295-307, 2017.

J. Ferrara, J. E. Levine, and P. Reddy, Graft-versus-host disease, Lancet, vol.373, pp.1550-1561, 2009.

B. H. Koehn and B. R. Blazar, Role of myeloid-derived suppressor cells in allogeneic hematopoietic cell transplantation, J Leukoc Biol, vol.102, pp.335-341, 2017.

B. R. Blazar, K. Macdonald, and G. R. Hill, Immune regulatory cell infusion for graft-versus-host disease prevention and therapy, Blood, vol.131, pp.2651-2660, 2018.

A. Luyckx, E. Schouppe, and O. Rutgeerts, G-CSF stem cell mobilization in human donors induces polymorphonuclear and mononuclear myeloid-derived suppressor cells, Clin Immunol, vol.143, pp.83-87, 2012.

A. Vendramin, S. Gimondi, and A. Bermema, Graft monocytic myeloid-derived suppressor cell content predicts the risk of acute graft-versus-host disease after allogeneic transplantation of granulocyte colony-stimulating factor-mobilized peripheral blood stem cells, Biol Blood Marrow Transplant, vol.20, pp.2049-2055, 2014.

M. Lv, X. Zhao, and Y. Hu, Monocytic and promyelocytic myeloidderived suppressor cells may contribute to G-CSF-induced immune tolerance in haplo-identical allogeneic hematopoietic stem cell transplantation, Am J Hematol, vol.90, pp.9-16, 2015.

J. Yin, C. Wang, and M. Huang, Circulating CD14(+) HLA-DR(À/low) myeloid-derived suppressor cells in leukemia patients with allogeneic hematopoietic stem cell transplantation: novel clinical potential strategies for the prevention and cellular therapy of graft-versushost disease, Cancer Med, vol.5, pp.1654-1669, 2016.

S. L. Highfill, P. C. Rodriguez, and Q. Zhou, Bone marrow myeloidderived suppressor cells (MDSCs) inhibit graft-versus-host disease (GVHD) via an arginase-1-dependent mechanism that is upregulated by interleukin-13, Blood, vol.116, pp.5738-5748, 2016.

D. Wang, Y. Yu, and K. Haarberg, Dynamic change and impact of myeloid-derived suppressor cells in allogeneic bone marrow transplantation in mice, Biol Blood Marrow Transplant, vol.19, pp.692-702, 2013.

L. Blanc, K. Jitschin, R. Mougiakakos, and D. , Myeloid-derived suppressor cells in allogeneic hematopoietic stem cell transplantation: a doubleedged sword?, Oncoimmunology, vol.2, pp.7-9, 2013.

S. Kusmartsev, F. Cheng, and B. Yu, All-trans-retinoic acid eliminates immature myeloid cells from tumor-bearing mice and improves the effect of vaccination, Cancer Res, vol.63, pp.4441-4449, 2003.

Y. Nefedova, M. Fishman, and S. Sherman, Mechanism of all-trans retinoic acid effect on tumor-associated myeloid-derived suppressor cells, Cancer Res, vol.67, pp.11021-11028, 2007.

J. Lee, J. Seo, and Y. Kim, The restoration of myeloid-derived suppressor cells as functional antigen-presenting cells by NKT cell help and all-trans-retinoic acid treatment, Int J Cancer, vol.131, pp.741-751, 2012.

C. Iclozan, A. S. Chiappori, and A. , Therapeutic regulation of myeloid-derived suppressor cells and immune response to cancer vaccine in patients with extensive stage small cell lung cancer, Cancer Immunol Immunother, vol.6, pp.247-253, 2009.

K. Tomihara, H. Fuse, and W. Heshiki, Gemcitabine chemotherapy induces phenotypic alterations of tumor cells that facilitate antitumor T cell responses in a mouse model of oral cancer, Oral Oncol, vol.50, pp.457-467, 2014.

N. E. Annels, V. E. Shaw, and R. F. Gabitass, The effects of gemcitabine and capecitabine combination chemotherapy and of low-dose adjuvant GM-CSF on the levels of myeloid-derived suppressor cells in patients with advanced pancreatic cancer, Cancer Immunol Immunother, vol.63, pp.175-183, 2014.

M. R. Porembka, J. B. Mitchem, and B. A. Belt, Pancreatic adenocarcinoma induces bone marrow mobilization of myeloid derived suppressor cells which promote primary tumor growth, Cancer Immunol Immunother, vol.61, pp.1373-1385, 2012.

J. Krejcik, T. Casneuf, and I. S. Nijhof, Daratumumab depletes CD38 + immune-regulatory cells, promotes T-cell expansion, and skews T-cell repertoire in multiple myeloma, Blood, vol.128, pp.384-395, 2016.

P. Trikha and W. E. Carson, Signaling pathways involved in MDSC regulation, Biochim Biophys Acta, vol.1846, pp.55-65, 2014.

J. Youn, V. Kumar, and M. Collazo, Epigenetic silencing of retinoblastoma gene regulates pathologic differentiation of myeloid cells in cancer, Nat immunol, vol.14, pp.211-220, 2013.

R. M. Stone, P. W. Manley, and R. A. Larson, Midostaurin: its odyssey from discovery to approval for treating acute myeloid leukemia and advanced systemic mastocytosis, Blood Adv, vol.2, pp.444-453, 2018.

B. R. Rosborough, L. R. Mathews, and B. M. Matta, FLT3 ligand mediates STAT3-independent expansion, but STAT-3 dependent activation of myeloid-derived suppressor cells, J Immunol, vol.192, pp.3470-3473, 2014.

A. Duffy, F. Zhao, and L. Haile, Comparative analysis of monocytic and granulocytic myeloid-derived suppressor cell subsets in patients with gastrointestinal malignancies, Cancer Immunol Immunother, vol.62, pp.299-307, 2013.

A. M. Bruger, A. Dorhoi, and G. Esendagli, How to measure the immunosuppressive activity of MDSC: assays, problems and potential solutions, Cancer Immunol Immunother, 2018.