Skip to main content

Advertisement

Log in

Myeloid-Derived Suppressor Cells in the Tumor Microenvironment: Current Knowledge and Future Perspectives

  • Review
  • Published:
Archivum Immunologiae et Therapiae Experimentalis Aims and scope

Abstract

The current knowledge on tumor-infiltrating myeloid-derived suppressor cells (MDSCs) is based mainly on the extensive work performed in murine models. Data obtained for human counterparts are generated on the basis of tumor analysis from patient samples. Both sources of information led to determination of the main suppressive mechanisms used by these cell subsets in tumor-bearing hosts. As a result of the identification of protein targets responsible for MDSCs suppressive activity, different therapeutics agents have been used to eliminate/reduce their adverse effect. In the present work, we review the current knowledge on suppressive mechanisms of MDSCs and therapeutic treatments that interfere with their differentiation, expansion or activity. Based on the accumulation of new evidences supporting their importance for tumor progression and metastasis, the interest in these cell types is increasing. We revise the methods of MDSC generation/differentiation ex vivo that may help in overcoming problems associated with limited numbers of cells available from animals and patients for their study.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  • Ahmad R, Raina D, Meyer C et al (2008) Triterpenoid CDDO-methyl ester inhibits the Janus-activated kinase-1 (JAK1)-->signal transducer and activator of transcription-3 (STAT3) pathway by direct inhibition of JAK1 and STAT3. Cancer Res 68:2920–2926

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Almand B, Clark JI, Nikitina E et al (2001) Increased production of immature myeloid cells in cancer patients: a mechanism of immunosuppression in cancer. J Immunol 166:678–689

    Article  CAS  PubMed  Google Scholar 

  • Apolloni E, Bronte V, Mazzoni A et al (2000) Immortalized myeloid suppressor cells trigger apoptosis in antigen-activated T lymphocytes. J Immunol 165:6723–6730

    Article  CAS  PubMed  Google Scholar 

  • Arce F, Breckpot K, Stephenson H et al (2011) Selective ERK activation differentiates mouse and human tolerogenic dendritic cells, expands antigen-specific regulatory T cells, and suppresses experimental inflammatory arthritis. Arthritis Rheum 63:84–95

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Baban B, Chandler PR, Sharma MD et al (2009) IDO activates regulatory T cells and blocks their conversion into Th17-like T cells. J Immunol 183:2475–2483

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Belladonna ML, Orabona C, Grohmann U et al (2009) TGF-beta and kynurenines as the key to infectious tolerance. Trends Mol Med 15:41–49

    Article  CAS  PubMed  Google Scholar 

  • Bill MA, Fuchs V, Li C et al (2010) The small molecule curcumin analog FLLL32 induces apoptosis in melanoma cells via STAT3 inhibition and retains the cellular response to cytokines with anti-tumor activity. Mol Cancer 9:165

    Article  PubMed  PubMed Central  Google Scholar 

  • Booth L, Roberts JL, Poklepovic A et al (2017) PDE5 inhibitors enhance the lethality of pemetrexed through inhibition of multiple chaperone proteins and via the actions of cyclic GMP and nitric oxide. Oncotarget 8:1449–1468

    PubMed  Google Scholar 

  • Bronte V, Wang M, Overwijk WW et al (1998) Apoptotic death of CD8+ T lymphocytes after immunization: induction of a suppressive population of Mac-1+/Gr-1+ cells. J Immunol 161:5313–5320

    CAS  PubMed  PubMed Central  Google Scholar 

  • Bronte V, Chappell DB, Apolloni E et al (1999) Unopposed production of granulocyte-macrophage colony-stimulating factor by tumors inhibits CD8+ T cell responses by dysregulating antigen-presenting cell maturation. J Immunol 162:5728–5737

    CAS  PubMed  PubMed Central  Google Scholar 

  • Chen MF, Kuan FC, Yen TC et al (2014) IL-6-stimulated CD11b+ CD14+ HLA-DR- myeloid-derived suppressor cells, are associated with progression and poor prognosis in squamous cell carcinoma of the esophagus. Oncotarget 5:8716–8728

    PubMed  PubMed Central  Google Scholar 

  • Corzo CA, Condamine T, Lu L et al (2010) HIF-1alpha regulates function and differentiation of myeloid-derived suppressor cells in the tumor microenvironment. J Exp Med 207:2439–2453

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • De Veirman K, Van Ginderachter JA, Lub S et al (2015) Multiple myeloma induces Mcl-1 expression and survival of myeloid-derived suppressor cells. Oncotarget 6:10532–10547

    Article  PubMed  PubMed Central  Google Scholar 

  • De Henau O, Rausch M, Winkler D et al (2016) Overcoming resistance to checkpoint blockade therapy by targeting PI3Kgamma in myeloid cells. Nature 539:443–447

    Article  PubMed  PubMed Central  Google Scholar 

  • De Vlaeminck Y, Gonzalez-Rascon A, Goyvaerts C et al (2016) Cancer-associated myeloid regulatory cells. Front Immunol 7:113

    Article  PubMed  PubMed Central  Google Scholar 

  • Ding X, Du H, MC Yoder MC et al (2014) Critical role of the mTOR pathway in development and function of myeloid-derived suppressor cells in lal-/- mice. Am J Pathol 184:397–408

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ding X, Wu L, Yan C et al (2015) Establishment of lal-/- myeloid lineage cell line that resembles myeloid-derived suppressive cells. PLoS One 10:e0121001

    Article  PubMed  PubMed Central  Google Scholar 

  • Dufait I, Schwarze JK, Liechtenstein T et al (2015) Ex vivo generation of myeloid-derived suppressor cells that model the tumor immunosuppressive environment in colorectal cancer. Oncotarget 6:12369–12382

    Article  PubMed  PubMed Central  Google Scholar 

  • Duwe AK, Singhal SK (1979a) The immunoregulatory role of bone marrow. I. Suppression of the induction of antibody responses to T-dependent and T-independent antigens by cells in the bone marrow. Cell Immunol 43:362–371

    Article  CAS  PubMed  Google Scholar 

  • Duwe AK, Singhal SK (1979b) The immunoregulatory role of bone marrow. II. Characterization of a suppressor cell inhibiting the in vitro antibody response. Cell Immunol 43:372–381

    Article  CAS  PubMed  Google Scholar 

  • Elliott LA, Doherty GA, Sheahan K et al (2017) Human tumor-infiltrating myeloid cells: phenotypic and functional diversity. Front Immunol 8:86

    Article  PubMed  PubMed Central  Google Scholar 

  • Escors D, Liechtenstein T, Perez-Janices N et al (2013) Assessing T-cell responses in anticancer immunohterapy: dendritic cells or myeloid-derived suppressor cells? Oncoimmunology 2:e26148

    Article  PubMed  PubMed Central  Google Scholar 

  • Fallarino F, Grohmann U, You S et al (2006) The combined effects of tryptophan starvation and tryptophan catabolites down-regulate T cell receptor zeta-chain and induce a regulatory phenotype in naive T cells. J Immunol 176:6752–6761

    Article  CAS  PubMed  Google Scholar 

  • Fujita M, Kohanbash G, Fellows-Mayle W et al (2011) COX-2 blockade suppresses gliomagenesis by inhibiting myeloid-derived suppressor cells. Cancer Res 71:2664–2674

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gabitass RF, Annels NE, Stocken DD et al (2011) Elevated myeloid-derived suppressor cells in pancreatic, esophageal and gastric cancer are an independent prognostic factor and are associated with significant elevation of the Th2 cytokine interleukin-13. Cancer Immunol Immunother 60:1419–1430

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gabrilovich DI, Velders MP, Sotomayor EM et al (2001) Mechanism of immune dysfunction in cancer mediated by immature Gr-1+ myeloid cells. J Immunol 166:5398–5406

    Article  CAS  PubMed  Google Scholar 

  • Gabrilovich DI, Bronte V, Chen SH et al (2007) The terminology issue for myeloid-derived suppressor cells. Cancer Res 67:425 author reply 426

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gehad AE, Lichtman MK, Schmults CD et al (2012) Nitric oxide-producing myeloid-derived suppressor cells inhibit vascular E-selectin expression in human squamous cell carcinomas. J Invest Dermatol 132:2642–2651

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Goh CC, Roggerson KM, Lee HC et al (2016) Hepatitis C virus-induced myeloid-derived suppressor cells suppress NK cell IFN-gamma production by altering cellular metabolism via arginase-1. J Immunol 196:2283–2292

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Grimm M, Spiecker M, De Caterina R et al (2002) Inhibition of major histocompatibility complex class II gene transcription by nitric oxide and antioxidants. J Biol Chem 277:26460–26467

    Article  CAS  PubMed  Google Scholar 

  • Hall B, Nakashima H, Sun ZJ et al (2013) Targeting of interleukin-13 receptor alpha2 for treatment of head and neck squamous cell carcinoma induced by conditional deletion of TGF-beta and PTEN signaling. J Transl Med 11:45

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hanson EM, Clements VK, Sinha P et al (2009) Myeloid-derived suppressor cells down-regulate L-selectin expression on CD4+ and CD8+ T cells. J Immunol 183:937–944

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Highfill SL, Rodriguez PC, Zhou Q et al (2010) Bone marrow myeloid-derived suppressor cells (MDSCs) inhibit graft-versus-host disease (GVHD) via an arginase-1-dependent mechanism that is up-regulated by interleukin-13. Blood 116:5738–5747

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hossain F, Al-Khami AA, Wyczechowska D et al (2015) Inhibition of fatty acid oxidation modulates immunosuppressive functions of myeloid-derived suppressor cells and enhances cancer therapies. Cancer Immunol Res 3:1236–1247

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Huang B, Pan PY, Li Q et al (2006) Gr-1+ CD115+ immature myeloid suppressor cells mediate the development of tumor-induced T regulatory cells and T-cell anergy in tumor-bearing host. Cancer Res 66:1123–1131

    Article  CAS  PubMed  Google Scholar 

  • Iclozan C, Antonia S, Chiappori A et al (2013) 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 62:909–918

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Keskinov AA, Shurin MR (2015) Myeloid regulatory cells in tumor spreading and metastasis. Immunobiology 220:236–242

    Article  CAS  PubMed  Google Scholar 

  • Ko JS, Zea AH, Rini BI et al (2009) Sunitinib mediates reversal of myeloid-derived suppressor cell accumulation in renal cell carcinoma patients. Clin Cancer Res 15:2148–2157

    Article  CAS  PubMed  Google Scholar 

  • Ko JS, Rayman P, Ireland J et al (2010) Direct and differential suppression of myeloid-derived suppressor cell subsets by sunitinib is compartmentally constrained. Cancer Res 70:3526–3536

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kodumudi KN, Woan K, Gilvary DL et al (2010) A novel chemoimmunomodulating property of docetaxel: suppression of myeloid-derived suppressor cells in tumor bearers. Clin Cancer Res 16:4583–4594

    Article  CAS  PubMed  Google Scholar 

  • Kortylewski M, Moreira D (2017) Myeloid cells as a target for oligonucleotide therapeutics: turning obstacles into opportunities. Cancer Immunol Immunother 66:979–988

    Article  CAS  PubMed  Google Scholar 

  • Lathers DM, Clark JI, Achille NJ et al (2004) Phase 1B study to improve immune responses in head and neck cancer patients using escalating doses of 25-hydroxyvitamin D3. Cancer Immunol Immunother 53:422–430

    Article  CAS  PubMed  Google Scholar 

  • Lechner MG, Liebertz DJ, Epstein AL (2010) Characterization of cytokine-induced myeloid-derived suppressor cells from normal human peripheral blood mononuclear cells. J Immunol 185:2273–2284

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Li H, Han Y, Guo Q et al (2009) Cancer-expanded myeloid-derived suppressor cells induce anergy of NK cells through membrane-bound TGF-beta 1. J Immunol 182:240–249

    Article  CAS  PubMed  Google Scholar 

  • Liechtenstein T, Perez-Janices N, Gato M et al (2014) A highly efficient tumor-infiltrating MDSC differentiation system for discovery of anti-neoplastic targets, which circumvents the need for tumor establishment in mice. Oncotarget 5:7843–7857

    Article  PubMed  PubMed Central  Google Scholar 

  • Lin L, Deangelis S, Foust E et al (2010) A novel small molecule inhibits STAT3 phosphorylation and DNA binding activity and exhibits potent growth suppressive activity in human cancer cells. Mol Cancer 9:217

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Long AH, Highfill SL, Cui Y et al (2016) Reduction of MDSCs with all-trans retinoic acid improves CAR therapy efficacy for sarcomas. Cancer Immunol Res 4:869–880

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lu P, Yu B, Xu J (2012) Cucurbitacin B regulates immature myeloid cell differentiation and enhances antitumor immunity in patients with lung cancer. Cancer Biother Radiopharm 27:495–503

    Article  CAS  PubMed  Google Scholar 

  • Marigo I, Bosio E, Solito S et al (2010) Tumor-induced tolerance and immune suppression depend on the C/EBPbeta transcription factor. Immunity 32:790–802

    Article  CAS  PubMed  Google Scholar 

  • Michels T, Shurin GV, Naiditch H et al (2012) Paclitaxel promotes differentiation of myeloid-derived suppressor cells into dendritic cells in vitro in a TLR4-independent manner. J Immunotoxicol 9:292–300

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Mirza N, Fishman M, Fricke I et al (2006) All-trans-retinoic acid improves differentiation of myeloid cells and immune response in cancer patients. Cancer Res 66:9299–9307

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Molon B, Ugel S, Del Pozzo F et al (2011) Chemokine nitration prevents intratumoral infiltration of antigen-specific T cells. J Exp Med 208:1949–1962

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Morales JK, Kmieciak M, Knutson KL et al (2010) GM-CSF is one of the main breast tumor-derived soluble factors involved in the differentiation of CD11b-Gr1- bone marrow progenitor cells into myeloid-derived suppressor cells. Breast Cancer Res Treat 123:39–49

    Article  CAS  PubMed  Google Scholar 

  • Moreira D, Zhang Q, Hossain DM et al (2015) TLR9 signaling through NF-kappaB/RELA and STAT3 promotes tumor-propagating potential of prostate cancer cells. Oncotarget 6:17302–17313

    Article  PubMed  PubMed Central  Google Scholar 

  • Mundy-Bosse BL, Young GS, Bauer T et al (2011) Distinct myeloid suppressor cell subsets correlate with plasma IL-6 and IL-10 and reduced interferon-alpha signaling in CD4(+) T cells from patients with GI malignancy. Cancer Immunol Immunother 60:1269–1279

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Munn DH, Sharma MD, Baban B et al (2005) GCN2 kinase in T cells mediates proliferative arrest and anergy induction in response to indoleamine 2,3-dioxygenase. Immunity 22:633–642

    Article  CAS  PubMed  Google Scholar 

  • Nagaraj S, Gupta K, Pisarev V et al (2007) Altered recognition of antigen is a mechanism of CD8 + T cell tolerance in cancer. Nat Med 13:828–835

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Nagaraj S, Youn JI, Weber H et al (2010) Anti-inflammatory triterpenoid blocks immune suppressive function of MDSCs and improves immune response in cancer. Clin Cancer Res 16:1812–1823

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Nanni S, Benvenuti V, Grasselli A et al (2009) Endothelial NOS, estrogen receptor beta, and HIFs cooperate in the activation of a prognostic transcriptional pattern in aggressive human prostate cancer. J Clin Invest 119:1093–1108

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Obermajer N, Kalinski P (2012) Generation of myeloid-derived suppressor cells using prostaglandin E2. Transplant Res 1:15

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Obermajer N, Muthuswamy R, Lesnock J et al (2011) Positive feedback between PGE2 and COX2 redirects the differentiation of human dendritic cells toward stable myeloid-derived suppressor cells. Blood 118:5498–5505

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Rao A, Taylor JL, Chi-Sabins N et al (2012) Combination therapy with HSP90 inhibitor 17-DMAG reconditions the tumor microenvironment to improve recruitment of therapeutic T cells. Cancer Res 72:3196–3206

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Reisser D, Onier-Cherix N, Jeannin JF (2002) Arginase activity is inhibited by L-NAME, both in vitro and in vivo. J Enzyme Inhib Med Chem 17:267–270

    Article  CAS  PubMed  Google Scholar 

  • Rodriguez PC, Quiceno DG, Zabaleta J et al (2004) Arginase I production in the tumor microenvironment by mature myeloid cells inhibits T-cell receptor expression and antigen-specific T-cell responses. Cancer Res 64:5839–5849

    Article  CAS  PubMed  Google Scholar 

  • Rodriguez PC, Quiceno DG, Ochoa AC (2007) l-Arginine availability regulates T-lymphocyte cell-cycle progression. Blood 109:1568–1573

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sakuishi K, Jayaraman P, Behar SM et al (2011) Emerging Tim-3 functions in antimicrobial and tumor immunity. Trends Immunol 32:345–349

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Santos L, Escande C, Denicola A (2016) Potential modulation of sirtuins by oxidative stress. Oxid Med Cell Longev 2016:9831825

    PubMed  Google Scholar 

  • Serafini P, Meckel K, Kelso M et al (2006) Phosphodiesterase-5 inhibition augments endogenous antitumor immunity by reducing myeloid-derived suppressor cell function. J Exp Med 203:2691–2702

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sevko A, Michels T, Vrohlings M et al (2013) Antitumor effect of paclitaxel is mediated by inhibition of myeloid-derived suppressor cells and chronic inflammation in the spontaneous melanoma model. J Immunol 190:2464–2471

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sharma MD, Baban B, Chandler P et al (2007) Plasmacytoid dendritic cells from mouse tumor-draining lymph nodes directly activate mature Tregs via indoleamine 2,3-dioxygenase. J Clin Invest 117:2570–2582

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sharma MD, Hou DY, Liu Y et al (2009) Indoleamine 2,3-dioxygenase controls conversion of Foxp3+ Tregs to TH17-like cells in tumor-draining lymph nodes. Blood 113:6102–6111

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sinha P, Clements VK, Fulton AM et al (2007) Prostaglandin E2 promotes tumor progression by inducing myeloid-derived suppressor cells. Cancer Res 67:4507–4513

    Article  CAS  PubMed  Google Scholar 

  • Sinha P, Okoro C, Foell D et al (2008) Proinflammatory S100 proteins regulate the accumulation of myeloid-derived suppressor cells. J Immunol 181:4666–4675

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Slavin S, Strober S (1979) Induction of allograft tolerance after total lymphoid irradiation (TLI): development of suppressor cells of the mixed leukocyte reaction (MLR). J Immunol 123:942–946

    CAS  PubMed  Google Scholar 

  • Slomiany BL, Slomiany A (2010) Mechanism of cytosolic phospholipase A(2) activation in ghrelin protection of salivary gland acinar cells against ethanol cytotoxicity. Adv Pharmacol Sci 2010:269274

  • Soliman HH, Minton SE, Han HS et al (2016) A phase I study of indoximod in patients with advanced malignancies. Oncotarget 7:22928–22938

    PubMed  PubMed Central  Google Scholar 

  • Srivastava MK, Sinha P, Clements VK et al (2010) Myeloid-derived suppressor cells inhibit T-cell activation by depleting cystine and cysteine. Cancer Res 70:68–77

    Article  CAS  PubMed  Google Scholar 

  • Sumida K, Wakita D, Narita Y et al (2012) Anti-IL-6 receptor mAb eliminates myeloid-derived suppressor cells and inhibits tumor growth by enhancing T-cell responses. Eur J Immunol 42:2060–2072

    Article  CAS  PubMed  Google Scholar 

  • Suzuki E, Kapoor V, Jassar AS et al (2005) Gemcitabine selectively eliminates splenic Gr-1+/CD11b + myeloid suppressor cells in tumor-bearing animals and enhances antitumor immune activity. Clin Cancer Res 11:6713–6721

    Article  CAS  PubMed  Google Scholar 

  • Talmadge JE, Gabrilovich DI (2013) History of myeloid-derived suppressor cells. Nat Rev Cancer 13:739–752

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Trikha P, Carson WE 3rd (2014) Signaling pathways involved in MDSC regulation. Biochim Biophys Acta 1846:55–65

    CAS  PubMed  PubMed Central  Google Scholar 

  • Tseng CW, Hung CF, Alvarez RD et al (2008) Pretreatment with cisplatin enhances E7-specific CD8+ T-cell-mediated antitumor immunity induced by DNA vaccination. Clin Cancer Res 14:3185–3192

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Tsuchiya Y, Igarashi M, Suzuki R et al (1988) Production of colony-stimulating factor by tumor cells and the factor-mediated induction of suppressor cells. J Immunol 141:699–708

    CAS  PubMed  Google Scholar 

  • Valenti R, Huber V, Filipazzi P et al (2006) Human tumor-released microvesicles promote the differentiation of myeloid cells with transforming growth factor-beta-mediated suppressive activity on T lymphocytes. Cancer Res 66:9290–9298

    Article  CAS  PubMed  Google Scholar 

  • Veltman JD, Lambers ME, van Nimwegen M et al (2010) COX-2 inhibition improves immunotherapy and is associated with decreased numbers of myeloid-derived suppressor cells in mesothelioma. Celecoxib influences MDSC function. BMC Cancer 10:464

    Article  PubMed  PubMed Central  Google Scholar 

  • Vincent J, Mignot G, Chalmin F et al (2010) 5-Fluorouracil selectively kills tumor-associated myeloid-derived suppressor cells resulting in enhanced T cell-dependent antitumor immunity. Cancer Res 70:3052–3061

    Article  CAS  PubMed  Google Scholar 

  • Wu L, Du H, Li Y et al (2011) Signal transducer and activator of transcription 3 (Stat3C) promotes myeloid-derived suppressor cell expansion and immune suppression during lung tumorigenesis. Am J Pathol 179:2131–2141

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Xiang X, Poliakov A, Liu C et al (2009) Induction of myeloid-derived suppressor cells by tumor exosomes. Int J Cancer 124:2621–2633

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Xiao G, Wang X, Sheng J et al (2015) Soluble NKG2D ligand promotes MDSC expansion and skews macrophage to the alternatively activated phenotype. J Hematol Oncol 8:13

    Article  PubMed  PubMed Central  Google Scholar 

  • Young MR, Aquino S, Young ME (1989) Differential induction of hematopoiesis and immune suppressor cells in the bone marrow versus in the spleen by Lewis lung carcinoma variants. J Leukoc Biol 45:262–273

    Article  CAS  PubMed  Google Scholar 

  • Zhao T, Du H, Ding X et al (2015) Activation of mTOR pathway in myeloid-derived suppressor cells stimulates cancer cell proliferation and metastasis in lal(−/−) mice. Oncogene 34:1938–1948

    Article  CAS  PubMed  Google Scholar 

  • Zhou J, Wu J, Chen X et al (2011) Icariin and its derivative, ICT, exert anti-inflammatory, anti-tumor effects, and modulate myeloid derived suppressive cells (MDSCs) functions. Int Immunopharmacol 11:890–898

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

This work was partially supported by a crowdfunding project by FECYT (Spain), a CAIXA grant, a BIOEF grant (Government of the Basque Country), a FIS grant (PI14/00579) from the Instituto de Salud Carlos III, and a grant from the Government of Navarre (BMED 033-2014), Spain. We thank SARAY foundation (Navarra, Spain) and Sandra Ibarra foundation (Spain) for their financial support. M. Gato is funded by a PhD fellowship granted by the Government of Navarre. M. Zuazo is funded by a fellowship granted by Universidad Publica de Navarra (UPNA), Spain. M. Ibáñez-Vea is funded by a Sara Borrel Fellowship. D. Escors is funded by a Miguel Servet Fellowship (CP12/03114) awarded by the Instituto de Salud Carlos III (Spain).

Author information

Authors and Affiliations

Authors

Corresponding authors

Correspondence to David Escors or Grazyna Kochan.

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Ibáñez-Vea, M., Zuazo, M., Gato, M. et al. Myeloid-Derived Suppressor Cells in the Tumor Microenvironment: Current Knowledge and Future Perspectives. Arch. Immunol. Ther. Exp. 66, 113–123 (2018). https://doi.org/10.1007/s00005-017-0492-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00005-017-0492-4

Keywords

Navigation