Monocytic Myeloid Derived Suppressor Cells in Hematological Malignancies

In the era of novel agents and immunotherapies in solid and liquid tumors, there is an emerging need to understand the cross-talk between the neoplastic cells, the host immune system, and the microenvironment to mitigate proliferation, survival, migration and resistance to drugs. In the microenvironment of hematological tumors there are cells belonging to the normal bone marrow, extracellular matrix proteins, adhesion molecules, cytokines, and growth factors produced by both stromal cells and neoplastic cells themselves. In this context, myeloid suppressor cells are an emerging sub-population of regulatory myeloid cells at different stages of differentiation involved in cancer progression and chronic inflammation. In this review, monocytic myeloid derived suppressor cells and their potential clinical implications are discussed to give a comprehensive vision of their contribution to lymphoproliferative and myeloid disorders.

[1]  A. Chiarenza,et al.  Immune off‐target effects of Brentuximab Vedotin in relapsed/refractory Hodgkin Lymphoma , 2019, British journal of haematology.

[2]  T. Guo,et al.  Myeloid-derived suppressor cells endow stem-like qualities to multiple myeloma cells by inducing piRNA-823 expression and DNMT3B activation , 2019, Molecular cancer.

[3]  S. Laszlo,et al.  Altered profile of immune regulatory cells in the peripheral blood of lymphoma patients , 2019, BMC Cancer.

[4]  Tae Woo Kim,et al.  Different role of circulating myeloid-derived suppressor cells in patients with multiple myeloma undergoing autologous stem cell transplantation , 2019, Journal of Immunotherapy for Cancer.

[5]  J. Moreaux,et al.  Myeloid-derived suppressor cells induce multiple myeloma cell survival by activating the AMPK pathway. , 2019, Cancer letters.

[6]  Q. Shen,et al.  Decitabine shows potent anti-myeloma activity by depleting monocytic myeloid-derived suppressor cells in the myeloma microenvironment , 2018, Journal of Cancer Research and Clinical Oncology.

[7]  A. Martner,et al.  Histamine targets myeloid-derived suppressor cells and improves the anti-tumor efficacy of PD-1/PD-L1 checkpoint blockade , 2018, Cancer Immunology, Immunotherapy.

[8]  R. Houot,et al.  Hide or defend, the two strategies of lymphoma immune evasion: potential implications for immunotherapy , 2018, Haematologica.

[9]  A. Romano,et al.  PMN-MDSC and arginase are increased in myeloma and may contribute to resistance to therapy , 2018, Expert review of molecular diagnostics.

[10]  Z. Vadasz,et al.  Hierarchical Involvement of Myeloid-Derived Suppressor Cells and Monocytes Expressing Latency-Associated Peptide in Plasma Cell Dyscrasias , 2018, Turkish journal of haematology : official journal of Turkish Society of Haematology.

[11]  R. Houot,et al.  Next-generation immunotherapies for lymphoma: one foot in the future , 2018, Annals of oncology : official journal of the European Society for Medical Oncology.

[12]  M. Gandhi,et al.  B cell lymphoma progression promotes the accumulation of circulating Ly6Clo monocytes with immunosuppressive activity , 2018, Oncoimmunology.

[13]  G. Li Volti,et al.  Monocytic myeloid‐derived suppressor cells as prognostic factor in chronic myeloid leukaemia patients treated with dasatinib , 2017, Journal of cellular and molecular medicine.

[14]  L. Ding,et al.  MiR‐30a increases MDSC differentiation and immunosuppressive function by targeting SOCS3 in mice with B‐cell lymphoma , 2017, The FEBS journal.

[15]  K. Tarte,et al.  Regulatory myeloid cells: an underexplored continent in B-cell lymphomas , 2017, Cancer Immunology, Immunotherapy.

[16]  A. Rosenwald,et al.  Prognostic relevance of CD163 and CD8 combined with EZH2 and gain of chromosome 18 in follicular lymphoma: a study by the Lunenburg Lymphoma Biomarker Consortium , 2017, Haematologica.

[17]  Xiaofang Wang,et al.  Mesenchymal stromal cells enhance the suppressive effects ofmyeloid-derived suppressor cells of multiple myeloma , 2017, Leukemia & lymphoma.

[18]  D. White,et al.  CML patients with deep molecular responses to TKI have restored immune effectors and decreased PD-1 and immune suppressors. , 2017, Blood.

[19]  D. Gabrilovich Myeloid-Derived Suppressor Cells , 2017, Cancer Immunology Research.

[20]  Daniel T. Fisher,et al.  Tumor-induced MDSC act via remote control to inhibit L-selectin-dependent adaptive immunity in lymph nodes , 2016, eLife.

[21]  R. Houot,et al.  Turning tumour cells into antigen presenting cells: The next step to improve cancer immunotherapy? , 2016, European journal of cancer.

[22]  R. Gascoyne,et al.  The combined role of biomarkers and interim PET scan in prediction of treatment outcome in classical Hodgkin's lymphoma: a retrospective, European, multicentre cohort study. , 2016, The Lancet. Haematology.

[23]  J. Finke,et al.  Myeloid-derived suppressor cells: The green light for myeloma immune escape. , 2016, Blood reviews.

[24]  S. Ostrand-Rosenberg,et al.  High‐mobility group box protein 1 promotes the survival of myeloid‐derived suppressor cells by inducing autophagy , 2016, Journal of leukocyte biology.

[25]  S. Pileri,et al.  The prognostic value of the myeloid-mediated immunosuppression marker Arginase-1 in classic Hodgkin lymphoma , 2016, Oncotarget.

[26]  E. Solary,et al.  CXCL12/CXCR4 pathway is activated by oncogenic JAK2 in a PI3K-dependent manner , 2016, Oncotarget.

[27]  Bie M. P. Verbist,et al.  Daratumumab depletes CD38+ immune regulatory cells, promotes T-cell expansion, and skews T-cell repertoire in multiple myeloma. , 2016, Blood.

[28]  Peter J. Murray,et al.  Recommendations for myeloid-derived suppressor cell nomenclature and characterization standards , 2016, Nature Communications.

[29]  Xiangyang Wu,et al.  Prognostic Significance of Monocytes and Monocytic Myeloid-Derived Suppressor Cells in Diffuse Large B-Cell Lymphoma Treated with R-CHOP , 2016, Cellular Physiology and Biochemistry.

[30]  Tae Woo Kim,et al.  Circulating immune cell phenotype can predict the outcome of lenalidomide plus low-dose dexamethasone treatment in patients with refractory/relapsed multiple myeloma , 2016, Cancer Immunology, Immunotherapy.

[31]  D. Ribatti,et al.  Multiple myeloma exosomes establish a favourable bone marrow microenvironment with enhanced angiogenesis and immunosuppression , 2016, The Journal of pathology.

[32]  F. Baron,et al.  Granulocytic myeloid-derived suppressor cells promote angiogenesis in the context of multiple myeloma , 2016, Oncotarget.

[33]  Jen-Chin Wang,et al.  Myeloid-derived suppressor cells in patients with myeloproliferative neoplasm. , 2016, Leukemia research.

[34]  G. Malerba,et al.  Identification of granulocytic myeloid-derived suppressor cells (G-MDSCs) in the peripheral blood of Hodgkin and non-Hodgkin lymphoma patients , 2016, Oncotarget.

[35]  A. Chiarenza,et al.  Granulocyte-like myeloid derived suppressor cells (G-MDSC) are increased in multiple myeloma and are driven by dysfunctional mesenchymal stem cells (MSC) , 2016, Oncotarget.

[36]  N. Hockstein,et al.  CD45 Phosphatase Inhibits STAT3 Transcription Factor Activity in Myeloid Cells and Promotes Tumor-Associated Macrophage Differentiation. , 2016, Immunity.

[37]  Amanda R. Campbell,et al.  Myeloid-Derived Suppressor Cells Express Bruton's Tyrosine Kinase and Can Be Depleted in Tumor-Bearing Hosts by Ibrutinib Treatment. , 2016, Cancer research.

[38]  K. Tarte,et al.  T-cell defect in diffuse large B-cell lymphomas involves expansion of myeloid-derived suppressor cells. , 2015, Blood.

[39]  K. Vanderkerken,et al.  The bone marrow microenvironment enhances multiple myeloma progression by exosome-mediated activation of myeloid-derived suppressor cells , 2015, Oncotarget.

[40]  Zhiping Wang,et al.  Prognostic significance of peripheral monocytic myeloid-derived suppressor cells and monocytes in patients newly diagnosed with diffuse large b-cell lymphoma. , 2015, International journal of clinical and experimental medicine.

[41]  A. Sica,et al.  RORC1 Regulates Tumor-Promoting "Emergency" Granulo-Monocytopoiesis. , 2015, Cancer cell.

[42]  H. Heslop,et al.  Tumor indoleamine 2,3-dioxygenase (IDO) inhibits CD19-CAR T cells and is downregulated by lymphodepleting drugs. , 2015, Blood.

[43]  D. Guc,et al.  Cancer associated fibroblasts have phenotypic and functional characteristics similar to the fibrocytes that represent a novel MDSC subset , 2015, Oncoimmunology.

[44]  S. A. Raccuia,et al.  Clinical Impact of the Immunome in Lymphoid Malignancies: The Role of Myeloid-Derived Suppressor Cells , 2015, Front. Oncol..

[45]  S. A. Raccuia,et al.  Myeloid Derived Suppressor Cells in Chronic Myeloid Leukemia , 2015, Front. Oncol..

[46]  R. Gascoyne,et al.  The Prognostic Impact of CD163-Positive Macrophages in Follicular Lymphoma: A Study from the BC Cancer Agency and the Lymphoma Study Association , 2015, Clinical Cancer Research.

[47]  H. Lokhorst,et al.  The impact of circulating suppressor cells in multiple myeloma patients on clinical outcome of DLIs , 2015, Bone Marrow Transplantation.

[48]  I. Bautmans,et al.  Multiple myeloma induces Mcl-1 expression and survival of myeloid-derived suppressor cells , 2015, Oncotarget.

[49]  U. Olsson‐Strömberg,et al.  The Tyrosine Kinase Inhibitors Imatinib and Dasatinib Reduce Myeloid Suppressor Cells and Release Effector Lymphocyte Responses , 2015, Molecular Cancer Therapeutics.

[50]  C. Vetro,et al.  Circulating myeloid‐derived suppressor cells correlate with clinical outcome in Hodgkin Lymphoma patients treated up‐front with a risk‐adapted strategy , 2015, British journal of haematology.

[51]  G. Barosi,et al.  Activation of non-canonical TGF-β1 signaling indicates an autoimmune mechanism for bone marrow fibrosis in primary myelofibrosis. , 2015, Blood cells, molecules & diseases.

[52]  Yiping Wang,et al.  Tumor-induced CD14+HLA-DR−/low myeloid-derived suppressor cells correlate with tumor progression and outcome of therapy in multiple myeloma patients , 2015, Cancer Immunology, Immunotherapy.

[53]  A. Dietz,et al.  Immune independent crosstalk between lymphoma and myeloid suppressor CD14+HLA-DRlow/neg monocytes mediates chemotherapy resistance , 2015, Oncoimmunology.

[54]  S. Fujii,et al.  Characterization of the myeloid-derived suppressor cell subset regulated by NK cells in malignant lymphoma , 2015, Oncoimmunology.

[55]  K. Zen,et al.  Role of Myeloid-Derived Suppressor Cells in Glucocorticoid-Mediated Amelioration of FSGS. , 2015, Journal of the American Society of Nephrology : JASN.

[56]  Liannv Qiu,et al.  CD14+HLA-DRlow/− expression: A novel prognostic factor in chronic lymphocytic leukemia , 2014, Oncology letters.

[57]  Xenia Geeraerts,et al.  Myeloid-Derived Suppressor Cells as Therapeutic Target in Hematological Malignancies , 2014, Front. Oncol..

[58]  S. Bicciato,et al.  Human fibrocytic myeloid‐derived suppressor cells express IDO and promote tolerance via Treg‐cell expansion , 2014, European journal of immunology.

[59]  K. Tracey,et al.  HMGB1 enhances immune suppression by facilitating the differentiation and suppressive activity of myeloid-derived suppressor cells. , 2014, Cancer research.

[60]  G. Barosi An Immune Dysregulation in MPN , 2014, Current Hematologic Malignancy Reports.

[61]  P. Brossart,et al.  Treatment with lenalidomide induces immunoactivating and counter‐regulatory immunosuppressive changes in myeloma patients , 2014, Clinical and experimental immunology.

[62]  P. Oefner,et al.  CLL-cells induce IDOhi CD14+HLA-DRlo myeloid-derived suppressor cells that inhibit T-cell responses and promote TRegs. , 2014, Blood.

[63]  P. Vigneri,et al.  Myeloid Derived Suppressor Cells (MDSCs) Are Increased and Exert Immunosuppressive Activity Together with Polymorphonuclear Leukocytes (PMNs) in Chronic Myeloid Leukemia Patients , 2014, PloS one.

[64]  R. Quarto,et al.  Chronic lymphocytic leukemia nurse-like cells express hepatocyte growth factor receptor (c-MET) and indoleamine 2,3-dioxygenase and display features of immunosuppressive type 2 skewed macrophages , 2014, Haematologica.

[65]  C. Vetro,et al.  Immunological Deregulation in Classic Hodgkin Lymphoma , 2014, Mediterranean journal of hematology and infectious diseases.

[66]  F. Raimondo,et al.  Immunological deregulation in classic hodgkin lymphoma. , 2014 .

[67]  T. Tadmor The growing link between multiple myeloma and myeloid derived suppressor cells , 2014, Leukemia & lymphoma.

[68]  Xin Wang,et al.  Up-regulated expression of indoleamine 2,3-dioxygenase 1 in non-Hodgkin lymphoma correlates with increased regulatory T-cell infiltration , 2014, Leukemia & lymphoma.

[69]  J. Chen,et al.  Lenalidomide enhances the protective effect of a therapeutic vaccine and reverses immune suppression in mice bearing established lymphomas , 2014, Leukemia.

[70]  N. Raje,et al.  Management of bone disease in multiple myeloma , 2014, Expert review of hematology.

[71]  S. Markovic,et al.  Absolute monocyte count at diagnosis and survival in mantle cell lymphoma , 2013, British journal of haematology.

[72]  A. Gallamini,et al.  Standard therapies versus novel therapies in Hodgkin lymphoma. , 2013, Immunology letters.

[73]  G. Morgan,et al.  Long-term Follow-up of MRC Myeloma IX Trial: Survival Outcomes with Bisphosphonate and Thalidomide Treatment , 2013, Clinical Cancer Research.

[74]  J. Khan,et al.  Fibrocytes represent a novel MDSC subset circulating in patients with metastatic cancer. , 2013, Blood.

[75]  J. Szer,et al.  Prognostic impact of monocyte count at presentation in mantle cell lymphoma , 2013, British journal of haematology.

[76]  F. Cavalli,et al.  Prognostic impact of monocyte count at presentation in mantle cell lymphoma , 2013, British journal of haematology.

[77]  J. Melo,et al.  Safety and efficacy of imatinib cessation for CML patients with stable undetectable minimal residual disease: results from the TWISTER study. , 2013, Blood.

[78]  L. Zitvogel,et al.  Mechanism of action of conventional and targeted anticancer therapies: reinstating immunosurveillance. , 2013, Immunity.

[79]  J. Markowitz,et al.  Myeloid derived suppressor cells – a new therapeutic target in the treatment of cancer , 2013, Journal of Immunotherapy for Cancer.

[80]  A. Polliack,et al.  Absolute monocytosis at diagnosis correlates with survival in diffuse large B‐cell lymphoma—possible link with monocytic myeloid‐derived suppressor cells , 2013, Hematological oncology.

[81]  N. Munshi,et al.  Tumor-promoting immune-suppressive myeloid-derived suppressor cells in the multiple myeloma microenvironment in humans. , 2013, Blood.

[82]  A. Martner,et al.  Myeloid-Derived Suppressor Cells Regulate Growth of Multiple Myeloma by Inhibiting T Cells in Bone Marrow , 2013, The Journal of Immunology.

[83]  A. Avilés,et al.  Randomized clinical trial of zoledronic acid in multiple myeloma patients undergoing high-dose chemotherapy and stem-cell transplantation. , 2013, Current oncology.

[84]  U. Olsson‐Strömberg,et al.  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 , 2013, PloS one.

[85]  S. Ponnazhagan,et al.  Myeloid-derived suppressor cells function as novel osteoclast progenitors enhancing bone loss in breast cancer. , 2013, Cancer research.

[86]  A. Cerwenka,et al.  Tumor-Infiltrating Monocytic Myeloid-Derived Suppressor Cells Mediate CCR5-Dependent Recruitment of Regulatory T Cells Favoring Tumor Growth , 2012, The Journal of Immunology.

[87]  I. Ghobrial,et al.  Monoclonal Gammopathy of Undetermined Significance and Smoldering Multiple Myeloma: A Review of the Current Understanding of Epidemiology, Biology, Risk Stratification, and Management of Myeloma Precursor Disease , 2012, Clinical Cancer Research.

[88]  K. Movahedi,et al.  Multiple myeloma induces the immunosuppressive capacity of distinct myeloid-derived suppressor cell subpopulations in the bone marrow , 2012, Leukemia.

[89]  P. Sinha,et al.  Cross-talk between myeloid-derived suppressor cells (MDSC), macrophages, and dendritic cells enhances tumor-induced immune suppression. , 2012, Seminars in cancer biology.

[90]  D. Gabrilovich,et al.  Coordinated regulation of myeloid cells by tumours , 2012, Nature Reviews Immunology.

[91]  A. Dietz,et al.  Association of an increased frequency of CD14+HLA‐DRlo/neg monocytes with decreased time to progression in chronic lymphocytic leukaemia (CLL) , 2012, British journal of haematology.

[92]  L. Kovarova,et al.  Induction by lenalidomide and dexamethasone combination increases regulatory cells of patients with previously untreated multiple myeloma , 2012, Leukemia & lymphoma.

[93]  O. Landgren,et al.  Multiple myeloma precursor disease: current clinical and epidemiological insights and future opportunities. , 2011, Oncology.

[94]  L. Zitvogel,et al.  Immunomodulatory effects of cyclophosphamide and implementations for vaccine design , 2011, Seminars in Immunopathology.

[95]  Hiroyasu Ito,et al.  Indoleamine 2,3-dioxygenase in tumor tissue indicates prognosis in patients with diffuse large B-cell lymphoma treated with R-CHOP , 2011, Annals of Hematology.

[96]  P. Zabel,et al.  Myeloid‐derived suppressor cells in the peripheral blood of cancer patients contain a subset of immature neutrophils with impaired migratory properties , 2011, Journal of leukocyte biology.

[97]  A. Dietz,et al.  Immunosuppressive CD14+HLA-DR(low)/- monocytes in B-cell non-Hodgkin lymphoma. , 2011, Blood.

[98]  Je-in Youn,et al.  The biology of myeloid‐derived suppressor cells: The blessing and the curse of morphological and functional heterogeneity , 2010, European journal of immunology.

[99]  T. Padhya,et al.  HIF-1α regulates function and differentiation of myeloid-derived suppressor cells in the tumor microenvironment , 2010, The Journal of experimental medicine.

[100]  G. Mundy,et al.  Gr-1+CD11b+ Myeloid-Derived Suppressor Cells: Formidable Partners in Tumor Metastasis , 2010, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[101]  Hiroyasu Ito,et al.  Serum concentration of L‐kynurenine predicts the clinical outcome of patients with diffuse large B‐cell lymphoma treated with R‐CHOP , 2010, European journal of haematology.

[102]  E. Celis,et al.  Mechanism of T Cell Tolerance Induced by Myeloid-Derived Suppressor Cells , 2010, The Journal of Immunology.

[103]  Pu Liu,et al.  Administration of Cyclophosphamide Changes the Immune Profile of Tumor-bearing Mice , 2010, Journal of immunotherapy.

[104]  P. Sinha,et al.  Myeloid-Derived Suppressor Cells Down-Regulate L-Selectin Expression on CD4+ and CD8+ T Cells1 , 2009, The Journal of Immunology.

[105]  R. Hayes,et al.  Monoclonal gammopathy of undetermined significance (MGUS) consistently precedes multiple myeloma: a prospective study. , 2009, Blood.

[106]  M. Atkins,et al.  Arginase I-producing myeloid-derived suppressor cells in renal cell carcinoma are a subpopulation of activated granulocytes. , 2009, Cancer research.

[107]  I. Borrello,et al.  Myeloid-derived suppressor cells promote cross-tolerance in B-cell lymphoma by expanding regulatory T cells. , 2008, Cancer research.

[108]  Z. Werb,et al.  Amino-biphosphonate-mediated MMP-9 inhibition breaks the tumor-bone marrow axis responsible for myeloid-derived suppressor cell expansion and macrophage infiltration in tumor stroma. , 2007, Cancer research.

[109]  J. Califano,et al.  Phosphodiesterase-5 inhibition augments endogenous antitumor immunity by reducing myeloid-derived suppressor cell function , 2006, The Journal of experimental medicine.

[110]  A. Migliaccio,et al.  Increased and pathologic emperipolesis of neutrophils within megakaryocytes associated with marrow fibrosis in GATA-1(low) mice. , 2004, Blood.

[111]  L. Staudt,et al.  Prediction of survival in follicular lymphoma based on molecular features of tumor-infiltrating immune cells. , 2004, The New England journal of medicine.

[112]  B. Fingleton,et al.  Expansion of myeloid immune suppressor Gr+CD11b+ cells in tumor-bearing host directly promotes tumor angiogenesis. , 2004, Cancer cell.

[113]  N. Munshi,et al.  Biologic sequelae of nuclear factor-kappaB blockade in multiple myeloma: therapeutic applications. , 2002, Blood.

[114]  A. Schmitt,et al.  Polymorphonuclear Neutrophil and Megakaryocyte Mutual Involvement in Myelofibrosis Pathogenesis , 2002, Leukemia & lymphoma.

[115]  S. Ostrand-Rosenberg,et al.  Myeloid-Derived Suppressor Cells: Critical Cells Driving Immune Suppression in the Tumor Microenvironment. , 2015, Advances in cancer research.

[116]  B. Bonnotte,et al.  Doxorubicin eliminates myeloid-derived suppressor cells and enhances the efficacy of adoptive T-cell transfer in breast cancer. , 2014, Cancer research.

[117]  D. Gabrilovich,et al.  Molecular mechanisms regulating myeloid-derived suppressor cell differentiation and function. , 2011, Trends in immunology.