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Int Immunopharmacol. Author manuscript; available in PMC Oct 22, 2012.
Published in final edited form as:
PMCID: PMC3478130

Myeloid derived suppressor cells in human diseases


Myeloid derived suppressor cells (MDSC) have been described as a heterogeneous cell population with potent immune suppressor function in mice. Limited data are available on MDSC in human diseases. Interpretation of these data is complicated by the fact that different markers have been used to analyze human MDSC subtypes in various clinical settings. Human MDSC are CD11b+, CD33+, HLA-DRneg/low and can be divided into granulocytic CD14 and monocytic CD14+ subtypes. Interleukin 4Rα, VEGFR, CD15 and CD66b have been suggested to be more specific markers for human MDSC, however these markers can only be found on some MDSC subsets. Until today the best marker for human MDSC remains their suppressor function, which can be either direct or indirect through the induction of regulatory T cells. Immune suppressor activity has been associated with high arginase 1 and iNOS activity as well as ROS production by MDSC. Not only in murine models, but even more importantly in patients with cancer, different drugs have been shown to either reverse the immune suppressor function of MDSC or directly target these cells. Systemic treatment with all-trans-retinoic acid has been shown to mature human MDSC and reverse their immune suppressor function. Alternatively, MDSC can be targeted by treatment with the multi-targeted receptor tyrosine kinase inhibitor sunitinib. In this review will provide a comprehensive summary of the recent literature on human MDSC.

Myeloid derived suppressor cells (MDSC) represent a heterogenous population of cells that consists of myeloid progenitor cells and immature myeloid cells (IMCs). Natural suppressor cells (the initial name for MDSC) were already described more than 25 years ago in patients with cancer [1] but in 1998 the interest in these cells was revived based on murine studies by Bronte and colleagues [2]. Murine MDSC are characterized by the expression of Gr-1 and CD11b. CD11b+Gr-1+ cells represent approximately 2 to 4 % of all nucleated splenocytes, but can increase up to 50% in tumor bearing mice [3, 4]. These cells are a mixture of immature myeloid cells, immature granulocytes, mononcytes-macrophages, dendritic cells and myeloid progenitor cells. Recently murine MDSC were further subdivided into two major groups: CD11b+Gr-1high granulocytic MDSC (which can also be identified as CD11b+Ly-6G+Ly6Clow MDSC) and CD11b+Gr-1low monocytic MDSC (which can also be identified as CD11b+Ly-6GLy6Chigh MDSC) [5]. We have previously identified CD49d as a marker to distinguish these two cell populations from each other and have shown that monocytic CD11b+CD49d+ MDSC were more potent suppressors of antigen-specific T cells in vitro than CD11b+CD49d granulocytic MDSC and suppressed T cell responses through an NO mediated mechanism [6]. Recently, murine MDSC have been further subdivided into 5 different classes dependent on the relative expression of CD11b and Gr-1 [7] and it is very likely that more subtypes and markers will be identified and described in the near future.

The heterogeneity of MDSC - which explains the lack of specific markers for these cells–is, along with their multiple suppressor function, [8] a hallmark of MDSC. Murine MDSC have been shown to suppress T cell responses by multiple mechanisms, which have recently been discussed in a comprehensive review [9]. L-arginine represents one important molecule central to the immune suppressive function by MDSC. L-arginine serves as a substrate for both iNOS and Arginase-1, which are both highly expressed in MDSC derived from tumor bearing mice. While utilizing L-arginine, iNOS generates nitric oxide (NO) and can suppress T cell function through different mechanisms. At the same time Arginase-1 depletes from T cells the essential amino acid L-arginine, which in turn leads to CD3 ζ-chain downregulation and cell cylce arrest through upregulation of cyclin D3 and cdk4 [10]. Reactive oxygen species (ROS) represent another suppressor mechanism and recently peroxynitrite has emerged as a crucial mediator of suppression of T cell function by MDSC, and which can lead, among other mechanisms, to nitration of the T-cell receptor and CD8 molecules [11].

Human MDSC subtypes

In humans CD34+ MDSC were reported for the first time in patients with head and neck cancer in 1995 [12]. In contrast to murine MDSC, which are defined by the expression of Gr-1 and CD11b, the corresponding cells in human are inadequately characterized because of the lack of uniform markers. An increased frequency of linCD33+CD34+CD15+ immature myeloid cells with immune suppressor function in peripheral blood from patients with head and neck cancer was reported [13] while others reported the suppressor function of CD15+ granulocytes [14]. In further studies human arginase-1 expressing MDSC were defined as CD11b+CD14+CD15+HLA-DRcells, which were found in the peripheral blood of patients with renal cancer [15]. Similarly, an increase in the frequency of linHLA-DRCD33+ cells was observed in renal cancer patients [16]. Based on our observations of an impaired function of CD1c+, CD19, CD14 myeloid dendritic cells in peripheral blood of patients with hepatocellular carcinoma (HCC)[17], we decided to also analyze the function of in vitro-generated dendritic cells from patients with HCC, which are usually derived from CD14+ monocytes. Here we observed that the function of dendritic cells was impaired in contrast to in vitro-generated dendritic cells from healthy controls. Further analysis demonstrated that a subtype of CD14+ monocytes, CD14+HLA-DRlow/neg cells, did not mature into functional dendritic cells and failed to induce an allo-response. Moreover, there was an increase in the frequency of this cell type in peripheral blood and tumor-infiltrating lymphocytes from HCC patients in comparison with healthy controls and control patients with other non-malignant liver diseases [18]. Further studies demonstrated that CD14+HLA-DRlow/neg cells suppressed proliferation and cytokine secretion of CD8+ T cells in an L- arginine-dependent manner and depletion of these cells in vitro unmasked antigen-specific T cell responses. Based on these findings CD14+HLA-DRlow/neg cells are MDSC. A similar cell type had previously been described in the context of melanoma patients vaccinated with an autologous tumor-derived heat shock protein peptide complex gp96 and low-dose GM-CSF [19] and was also found in melanoma patients without specific treatment [20]. Based on these initial studies MDSC were analyzed in a number of different other tumor settings and their phenotype was further characterized (Table 1).

Table 1
MDSC subtypes in human disease

Phenotypical analysis of human MDSC

While murine MDSC subtypes can be divided into a more granulocytic and a monocytic cell type, attempts have been made to also divide human MDSC into a more granulocytic and a monocytic cell type. Both MDSC subtypes express the common myeloid markers CD11b and CD33 but lack expression of markers of mature myeloid cells such as CD40, CD80, CD83 and HLA-DR. It has been suggested that monocytic MDSC are CD14+ and granulocytic MDSC express CD15, while both groups of MDSC are HLA-DRlow/neg and CD33+. However, more data is needed to corroborate this hypothesis on human MDSC. Similar to murine studies [4], IL-4Ra has been suggested as a specific marker for tumor derived MDSC with suppressor function [21], however this marker has not been evaluated extensively. VEGF-R is another marker, which has recently been described to be expressed on MDSC, which could also explain the effect of certain targeted therapies on MDSC [21, 22] (see below). Future studies will aim at the identification of better markers to distinguish CD14+HLA-DR+ moncytes from CD14+HLA-DRlow/neg MDSC.

In vitro generated MDSC

Recently a number of protocols have been described to generate MDSC from mice bone marrow [23, 24]. Mouse bone marrow-derived IL4Rα+ MDSC which consist of a mixture of immature cells have been shown to posess immune suppressor activity, and can be derived with GM-CSF+G-CSF or GM-CSF+IL-6 or IL-13 [23, 25]. Two different approaches were taken to mimic the situation in a cancer patient in order to induce MDSC. In one setting, CD14+ monocytes isolated from healthy donors were differentiated with IL4 and GM-CSF in the presence of tumor-derived microvesicles. This led to the induction of CD14+HLA-DRneg/low MDSC with suppressor activity [26]. In a different setting, PBMC from healthy donors were incubated in the presence of factors known to be implicated in the generation and activation of MDSC. In this study it was shown that human MDSC can be induced after incubation of PBMC with GM-CSF+IL-6 or GM-CSF + IL-1β, PGE2, TNF-α and VEGF [27]. In vitro-generated MDSC were potent suppressors of T cell responses and were CD33+, HLA-DRlow, CD11b+ and CD66b+. Future studies are needed to further investigate the possibility of using these cells for adoptive therapy in different autoimmune settings such as graft versus host disease [25].

MDSC in non-tumor settings

Human MDSC have been described in patients with different tumors (Table 1). However, in murine settings MDSC have been described also in a number of different non-malignant settings such as during bacterial [9], viral [28] and parasitic infections [29], traumatic stress [30] sepsis [31], acute inflammation [7], tolerance [32], graft versus host disease [25] and different autoimmune diseases such as diabetes [33], encephalomyelitis [34] and colitis [6]. Until today, only limited data is available on human MDSC in non-tumor settings. We have described an increase in the frequency of CD14+HLA-DRlow/neg MDSC in patients with inflammatory bowel diseases [6] and are currently in the process of analyzing MDSC in this disease in more detail.

Suppressive Mechanisms of human MDSC

Multiple mechanisms have been suggested to be implicated in suppressor activity of murine MDSC and are discussed in recent reviews [9, 35]. In contrast, only limited information is available on how human MDSC exert their suppressor function. One of the first mechanisms for MDSC-mediated T cell suppression in mice has been associated with the metabolism of L-arginine, which serves as a substrate for two enzymes: arginase 1 and iNOS. Both enzymes have been shown to be highly expressed in murine MDSC and to inhibit T cell function. Therefore both ways were also investigated in human MDSC and indeed, were shown to be involved in suppression of T cell responses in vitro by human MDSC. MDSC were shown to have elevated arginase activity, which was associated with a decreased CD3ζ chain expression on T cells [14, 15]. NOHA, an arginase inhibitor, and L-NMMA, a potent arginase and NOS2 inhibitor respectively, were able to block MLR suppressor activity of MDSC [36]. Addition of exogenous L-arginine was able to restore IFN-γ release by T cells when co-cultured with CD14+HLA-DRlow/neg MDSC [18]. To delineate the suppressive mechanisms used by CD14+HLA-DRlow/neg MDSC from melanoma patients, quantitative PCR analysis for candidate suppressive molecules (arginase-1, COX-2, IDO, IL-10, i-NOS and TGF-b) was performed. Arg1 was expressed at significantly higher levels in patient-derived CD14+HLA-DRlow/neg MDSC, whereas levels of COX 2 and iNOS transcription were significantly lower. No difference in indoleamine 2,3-dioxygenase, IL-10, and TGF-α expression was observed. Inhibition of arginase also improved T-cell proliferation indicating the dominance of this pathway for MDSC mediated inhibition of T cells [37]. However, ROS-mediated suppression of T cell responses has also been shown to be active in CD14+HLA-DRlow/neg MDSC in this study. Similarly, CD11b+CD14CD33+ MDSC have been shown to mediate immune suppression by ROS production [38, 39]. Finally, while TGF-β release by CD14+HLA-DRlow/neg cells could be demonstrated when MDSC from melanoma patients were analyzed [19], we could only detect membrane bound TGF-β on MDSC (unpublished data).

Multiple different biological mechanisms have been suggested how murine MDSC suppress immune responses and promote tumor development [8]. These mechanisms include direct inhibition of T cells as discussed above but also indirect immune inhibitory effects. Recently Gabrilovich’s group could demonstrate that MDSC from peripheral blood suppress T cells in an antigen specific manner whereas MDSC from the tumor site suppress T cells in a non-specific manner [40]. Our laboratory has shown one indirect method of how MDSC exert their suppressor function. We have examined the effect of in CD14+HLA-DRlow/neg MDSC on naïve CD4+ T cells in vitro. In contrast to CD14+HLA-DR+ monocytes CD14+HLA-DRlow/neg, MDSC triggered release of IL-10 by CD4+ T cells and induced the induction of regulatory T cells [18]. Currently we are examining what factors are essential for the induction of regulatory T cells by MDSC and if these markers can be used to distinguish CD14+HLA-DRlow/neg MDSC from CD14+HLA-DR+ monocytes.

MDSC NK interaction

NK cells and NKT cells play important roles in innate immune responses. NK cells have shown to be involved in the first defense and regulation of adaptive immune system through the action on APCs. Therefore it is important to understand NK-MDSC interactions. It has been suggested that murine NKT cells facilitate the conversion of immunosuppressive MDSC into immunogenic APCs [41]. Conflicting results have been described on the effect of MDSC on NK cell function in murine tumor models. Different studies demonstrated an inhibition of NK cell function [42, 43]. In one study this inhibition was mediated via membrane-bound TGF-b1 [43], while others report an unexpected activating role of MDSC on NK cells [44], possibly regulated through STAT-1 [45]. In a different study the absence of invariant NKT (iNKT) cells in mice during influenza A virus infection resulted in the expansion of MDSC leading to high IAV titer and increased mortality [36]. Only one study has examined NK-MDSC crosstalk in humans. We have been able to show that NK cell function was impaired in patients with HCC. In in vitro studies we showed that MDSC impaired NK cell function, and the depletion of MDSC from PBMC led to an improvement in NK cell lysis, suggesting that the observed increase of MDSC in patients with HCC might be one possible reason for impaired NK cell function. Interestingly, suppression of NK cells was not arginase-1-, iNOS- or ROS mediated, but rather, blockade of NKp30 could partially reverse the inhibitory function of human MDSC on NK cells in vitro [46].

Targeting MDSC in patients with cancer

Since MDSC are still a very poorly defined cell population it will be difficult to specifically target these cells in cancer patients with the aim of engaging tumor-specific immune responses. Nevertheless, a number of different approaches have already been evaluated with the aim of boosting immune responses by targeting MDSC. In one of the first studies reported, 18 patients with metastatic renal cell carcinoma were treated with all-trans-retinoic acid (ATRA) followed by s.c. interleukin 2 (IL-2) based on in vitro studies, which suggested that ATRA matures MDSC [39, 47]. A reduction in the number of Lin HLA-DR CD33+ cells accompanied by an improvement of tetanus-toxoid-specific T-cell response was observed [16]. Sunitinib, which is currently being used for the treatment of renal cancer also demonstrated effects on human MDSC. Both circulating CD33+HLA-DR and CD15+CD14- MDSC declined in response to treatment with sunitinib. In parallel an increase in IFN-g production upon CD3 stimulation by T cells was observed [48]. In contrast, treatment of RCC patients with the anti-VEGF antibody bevacizumab, did not reduce the accumulation of MDSC in peripheral blood [22], despite preclinical data suggesting that VEGF can induce MDSC. Finally, Vitamin D3 has been shown to reduce the number of immune suppressive CD34+ cells and to increase HLA-DR expression on PBMC in HNSCC patients.


MDSC have gained a lot of attention in recent years mainly in the tumor immunology community. However, based on the results from murine studies in non-tumor settings, human MDSC will need to be analyzed in more detail in non-cancer patients as well. One major hurdle remains the heterogeneity of the cells. The only possibility of overcoming this problem will be through a thorough phenotypical and functional analysis of all potential MDSC subsets in different clinical settings. Identification of better markers will facilitate these studies. More in-depth analysis of the interaction of MDSC with other cell types will help understand the biological function and, finally, the specific targeting of human MDSC and their subtypes will help the effect of immune-based therapies in cancer.

Table 2
Phenotypical analysis of human MDSC (p/n: two populations: positive and/or negative; int: intermediate; l/n: low or negative; hi: high).
Table 3
Medical targeting of MDSC#


The authors’ work was supported by the Initiative and Networking Fund of the Helmholtz Association within the Helmholtz Alliance on Immunotherapy of Cancer (M.P.M.) and in part by the Intramural Research Program of the Center for Cancer Research, National Cancer Institute (NCI), National Institutes of Health (T.F.G.)


1. Young MR, Newby M, Wepsic HT. Hematopoiesis and suppressor bone marrow cells in mice bearing large metastatic Lewis lung carcinoma tumors. Cancer Res. 1987;47:100–5. [PubMed]
2. Bronte V, Wang M, Overwijk WW, Surman DR, Pericle F, Rosenberg SA, et al. Apoptotic death of CD8+ T lymphocytes after immunization: induction of a suppressive population of Mac-1+/Gr-1+ cells. J Immunol. 1998;161:5313–20. [PMC free article] [PubMed]
3. Zhao F, Obermann S, von Wasielewski R, Haile L, Manns MP, Korangy F, et al. Increase in frequency of myeloid-derived suppressor cells in mice with spontaneous pancreatic carcinoma. Immunology. 2009;128:141–9. [PMC free article] [PubMed]
4. Gallina G, Dolcetti L, Serafini P, De Santo C, Marigo I, Colombo MP, et al. Tumors induce a subset of inflammatory monocytes with immunosuppressive activity on CD8+ T cells. J Clin Invest. 2006;116:2777–90. [PMC free article] [PubMed]
5. Youn JI, Gabrilovich D. The biology of myeloid-derived suppressor cells: The blessing and the curse of morphological and functional heterogeneity. Eur J Immunol. 2010 in press. [PMC free article] [PubMed]
6. Haile LA, von Wasielewski R, Gamrekelashvili J, Kruger C, Bachmann O, Westendorf AM, et al. Myeloid-derived suppressor cells in inflammatory bowel disease: a new immunoregulatory pathway. Gastroenterology. 2008;135:871–81. 81, e1–5. [PubMed]
7. Greifenberg V, Ribechini E, Rossner S, Lutz MB. Myeloid-derived suppressor cell activation by combined LPS and IFN-gamma treatment impairs DC development. Eur J Immunol. 2009;39:2865–76. [PubMed]
8. Ostrand-Rosenberg S. Myeloid-derived suppressor cells: more mechanisms for inhibiting antitumor immunity. Cancer Immunol Immunother. 2010 [PMC free article] [PubMed]
9. Gabrilovich DI, Nagaraj S. Myeloid-derived suppressor cells as regulators of the immune system. Nat Rev Immunol. 2009;9:162–74. [PMC free article] [PubMed]
10. Rodriguez PC, Quiceno DG, Ochoa AC. L-arginine availability regulates T-lymphocyte cell-cycle progression. Blood. 2007;109:1568–73. [PMC free article] [PubMed]
11. Nagaraj S, Gupta K, Pisarev V, Kinarsky L, Sherman S, Kang L, et al. Altered recognition of antigen is a mechanism of CD8(+) T cell tolerance in cancer. Nat Med. 2007;13:828–35. [PMC free article] [PubMed]
12. Pak AS, Wright MA, Matthews JP, Collins SL, Petruzzelli GJ, Young MR. Mechanisms of immune suppression in patients with head and neck cancer: presence of CD34(+) cells which suppress immune functions within cancers that secrete granulocyte-macrophage colony-stimulating factor. Clin Cancer Res. 1995;1:95–103. [PubMed]
13. Almand B, Clark JI, Nikitina E, van Beynen J, English NR, Knight SC, et al. Increased production of immature myeloid cells in cancer patients: a mechanism of immunosuppression in cancer. J Immunol. 2001;166:678–89. [PubMed]
14. Schmielau J, Finn OJ. Activated granulocytes and granulocyte-derived hydrogen peroxide are the underlying mechanism of suppression of t-cell function in advanced cancer patients. Cancer Res. 2001;61:4756–60. [PubMed]
15. Zea AH, Rodriguez PC, Atkins MB, Hernandez C, Signoretti S, Zabaleta J, et al. Arginase-producing myeloid suppressor cells in renal cell carcinoma patients: a mechanism of tumor evasion. Cancer Res. 2005;65:3044–8. [PubMed]
16. Mirza N, Fishman M, Fricke I, Dunn M, Neuger AM, Frost TJ, et al. All-trans-retinoic acid improves differentiation of myeloid cells and immune response in cancer patients. Cancer Res. 2006;66:9299–307. [PMC free article] [PubMed]
17. Ormandy LA, Farber A, Cantz T, Petrykowska S, Wedemeyer H, Horning M, et al. Direct ex vivo analysis of dendritic cells in patients with hepatocellular carcinoma. World J Gastroenterol. 2006;12:3275–82. [PMC free article] [PubMed]
18. Hoechst B, Ormandy LA, Ballmaier M, Lehner F, Kruger C, Manns MP, et al. A new population of myeloid-derived suppressor cells in hepatocellular carcinoma patients induces CD4(+)CD25(+)Foxp3(+) T cells. Gastroenterology. 2008;135:234–43. [PubMed]
19. Filipazzi P, Valenti R, Huber V, Pilla L, Canese P, Iero M, et al. Identification of a new subset of myeloid suppressor cells in peripheral blood of melanoma patients with modulation by a granulocyte-macrophage colony-stimulation factor-based antitumor vaccine. J Clin Oncol. 2007;25:2546–53. [PubMed]
20. Ugurel S, Uhlig D, Pfohler C, Tilgen W, Schadendorf D, Reinhold U. Down-regulation of HLA class II and costimulatory CD86/B7-2 on circulating monocytes from melanoma patients. Cancer Immunol Immunother. 2004;53:551–9. [PubMed]
21. Mandruzzato S, Solito S, Falisi E, Francescato S, Chiarion-Sileni V, Mocellin S, et al. IL4Ralpha+ myeloid-derived suppressor cell expansion in cancer patients. J Immunol. 2009;182:6562–8. [PubMed]
22. Rodriguez PC, Ernstoff MS, Hernandez C, Atkins M, Zabaleta J, Sierra R, et al. Arginase I-producing myeloid-derived suppressor cells in renal cell carcinoma are a subpopulation of activated granulocytes. Cancer Res. 2009;69:1553–60. [PMC free article] [PubMed]
23. Marigo I, Bosio E, Solito S, Mesa C, Fernandez A, Dolcetti L, et al. Tumor-induced tolerance and immune suppression depend on the C/EBPbeta transcription factor. Immunity. 2010;32:790–802. [PubMed]
24. Zhou Z, French DL, Ma G, Eisenstein S, Chen Y, Divino CM, et al. Development and function of myeloid-derived suppressor cells generated from mouse embryonic and hematopoietic stem cells. Stem Cells. 2010;28:620–32. [PubMed]
25. Highfill SL, Rodriguez PC, Zhou Q, Goetz CA, Koehn BH, Veenstra R, et al. 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. 2010;116:5738–47. [PMC free article] [PubMed]
26. Valenti R, Huber V, Filipazzi P, Pilla L, Sovena G, Villa A, et al. Human tumor-released microvesicles promote the differentiation of myeloid cells with transforming growth factor-beta-mediated suppressive activity on T lymphocytes. Cancer Res. 2006;66:9290–8. [PubMed]
27. Lechner MG, Liebertz DJ, Epstein AL. Characterization of Cytokine-Induced Myeloid-Derived Suppressor Cells from Normal Human Peripheral Blood Mononuclear Cells. J Immunol. 2010 [PMC free article] [PubMed]
28. Bowen JL, Olson JK. Innate immune CD11b+Gr-1+ cells, suppressor cells, affect the immune response during Theiler’s virus-induced demyelinating disease. J Immunol. 2009;183:6971–80. [PubMed]
29. Van Ginderachter JA, Beschin A, De Baetselier P, Raes G. Myeloid-derived suppressor cells in parasitic infections. Eur J Immunol. 2010;40:2976–85. [PubMed]
30. Cuenca AG, Delano MJ, Kelly-Scumpia KM, Moreno C, Scumpia PO, Laface DM, et al. A Paradoxical Role for Myeloid Derived Suppressor Cells in Sepsis and Trauma. Mol Med. 2010 [PMC free article] [PubMed]
31. Delano MJ, Scumpia PO, Weinstein JS, Coco D, Nagaraj S, Kelly-Scumpia KM, et al. MyD88-dependent expansion of an immature GR-1+CD11b+ population induces T cell suppression and Th2 polarization in sepsis. J Exp Med. 2007 [PMC free article] [PubMed]
32. Dugast AS, Haudebourg T, Coulon F, Heslan M, Haspot F, Poirier N, et al. Myeloid-derived suppressor cells accumulate in kidney allograft tolerance and specifically suppress effector T cell expansion. J Immunol. 2008;180:7898–906. [PubMed]
33. Yin B, Ma G, Yen CY, Zhou Z, Wang GX, Divino CM, et al. Myeloid-derived suppressor cells prevent type 1 diabetes in murine models. J Immunol. 2010;185:5828–34. [PubMed]
34. Zhu B, Bando Y, Xiao S, Yang K, Anderson AC, Kuchroo VK, et al. CD11b+Ly-6Chi suppressive monocytes in experimental autoimmune encephalomyelitis. J Immunol. 2007;179:5228–37. [PubMed]
35. Bronte V, Mocellin S. Suppressive influences in the immune response to cancer. J Immunother. 2009;32:1–11. [PubMed]
36. De Santo C, Salio M, Masri SH, Lee LY, Dong T, Speak AO, et al. Invariant NKT cells reduce the immunosuppressive activity of influenza A virus-induced myeloid-derived suppressor cells in mice and humans. J Clin Invest. 2008;118:4036–48. [PMC free article] [PubMed]
37. Poschke I, Mougiakakos D, Hansson J, Masucci GV, Kiessling R. Immature Immunosuppressive CD14+HLA-DR-/low Cells in Melanoma Patients Are Stat3hi and Overexpress CD80, CD83, and DC-Sign. Cancer Res. 2010 [PubMed]
38. Corzo CA, Cotter MJ, Cheng P, Cheng F, Kusmartsev S, Sotomayor E, et al. Mechanism regulating reactive oxygen species in tumor-induced myeloid-derived suppressor cells. J Immunol. 2009;182:5693–701. [PMC free article] [PubMed]
39. Kusmartsev S, Su Z, Heiser A, Dannull J, Eruslanov E, Kubler H, et al. Reversal of myeloid cell-mediated immunosuppression in patients with metastatic renal cell carcinoma. Clin Cancer Res. 2008;14:8270–8. [PubMed]
40. Corzo CA, Condamine T, Lu L, Cotter MJ, Youn JI, Cheng P, et al. HIF-1alpha regulates function and differentiation of myeloid-derived suppressor cells in the tumor microenvironment. J Exp Med. 2010;207:2439–53. [PMC free article] [PubMed]
41. Ko HJ, Lee JM, Kim YJ, Kim YS, Lee KA, Kang CY. Immunosuppressive myeloid-derived suppressor cells can be converted into immunogenic APCs with the help of activated NKT cells: an alternative cell-based antitumor vaccine. J Immunol. 2009;182:1818–28. [PubMed]
42. Suzuki E, Kapoor V, Jassar AS, Kaiser LR, Albelda SM. Gemcitabine Selectively Eliminates Splenic Gr-1+/CD11b+ Myeloid Suppressor Cells in Tumor-Bearing Animals and Enhances Antitumor Immune Activity. Clin Cancer Res. 2005;11:6713–21. [PubMed]
43. Li H, Han Y, Guo Q, Zhang M, Cao X. Cancer-Expanded Myeloid-Derived Suppressor Cells Induce Anergy of NK Cells through Membrane-Bound TGF-{beta}1. J Immunol. 2009;182:240–9. [PubMed]
44. Nausch N, Galani IE, Schlecker E, Cerwenka A. Mononuclear Myeloid-Derived “Suppressor” Cells express RAE-1 and activate NK cells. Blood. 2008 [PMC free article] [PubMed]
45. Liu C, Yu S, Kappes J, Wang J, Grizzle WE, Zinn KR, et al. Expansion of spleen myeloid suppressor cells represses NK cell cytotoxicity in tumor-bearing host. Blood. 2007;109:4336–42. [PMC free article] [PubMed]
46. Hoechst B, Voigtlaender T, Ormandy L, Gamrekelashvili J, Zhao F, Wedemeyer H, et al. Myeloid derived suppressor cells inhibit natural killer cells in patients with hepatocellular carcinoma via the NKp30 receptor. Hepatology. 2009;50:799–807. [PubMed]
47. Gabrilovich DI, Velders MP, Sotomayor EM, Kast WM. Mechanism of immune dysfunction in cancer mediated by immature Gr-1+ myeloid cells. J Immunol. 2001;166:5398–406. [PubMed]
48. Ko JS, Zea AH, Rini BI, Ireland JL, Elson P, Cohen P, et al. Sunitinib mediates reversal of myeloid-derived suppressor cell accumulation in renal cell carcinoma patients. Clin Cancer Res. 2009;15:2148–57. [PubMed]
49. Daud AI, Mirza N, Lenox B, Andrews S, Urbas P, Gao GX, et al. Phenotypic and functional analysis of dendritic cells and clinical outcome in patients with high-risk melanoma treated with adjuvant granulocyte macrophage colony-stimulating factor. J Clin Oncol. 2008;26:3235–41. [PubMed]
50. Diaz-Montero CM, Salem ML, Nishimura MI, Garrett-Mayer E, Cole DJ, Montero AJ. Increased circulating myeloid-derived suppressor cells correlate with clinical cancer stage, metastatic tumor burden, and doxorubicin-cyclophosphamide chemotherapy. Cancer Immunol Immunother. 2008 [PMC free article] [PubMed]
51. Liu CY, Wang YM, Wang CL, Feng PH, Ko HW, Liu YH, et al. Population alterations of L: -arginase- and inducible nitric oxide synthase-expressed CD11b(+)/CD14 (−)/CD15 (+)/CD33 (+) myeloid-derived suppressor cells and CD8 (+) T lymphocytes in patients with advanced-stage non-small cell lung cancer. J Cancer Res Clin Oncol. 2010;110:36–45. [PubMed]
52. Srivastava MK, Bosch JJ, Thompson JA, Ksander BR, Edelman MJ, Ostrand-Rosenberg S. Lung cancer patients’ CD4(+) T cells are activated in vitro by MHC II cell-based vaccines despite the presence of myeloid-derived suppressor cells. Cancer Immunol Immunother. 2008;57:1493–504. [PMC free article] [PubMed]
53. Brimnes MK, Vangsted AJ, Knudsen LM, Gimsing P, Gang AO, Johnsen HE, et al. Increased level of both CD4+FOXP3+ regulatory T cells and CD14+HLA-DR/low myeloid-derived suppressor cells and decreased level of dendritic cells in patients with multiple myeloma. Scand J Immunol. 2010;72:540–7. [PubMed]
54. Vuk-Pavlovic S, Bulur PA, Lin Y, Qin R, Szumlanski CL, Zhao X, et al. Immunosuppressive CD14+HLA-DRlow/− monocytes in prostate cancer. Prostate. 2010;70:443–55. [PMC free article] [PubMed]
55. van Cruijsen H, van der Veldt AA, Vroling L, Oosterhoff D, Broxterman HJ, Scheper RJ, et al. Sunitinib-induced myeloid lineage redistribution in renal cell cancer patients: CD1c+ dendritic cell frequency predicts progression-free survival. Clin Cancer Res. 2008;14:5884–92. [PubMed]
56. Serafini P, Meckel K, Kelso M, Noonan K, Califano J, Koch W, et al. Phosphodiesterase-5 inhibition augments endogenous antitumor immunity by reducing myeloid-derived suppressor cell function. J Exp Med. 2006;203:2691–702. [PMC free article] [PubMed]
57. Brandau S, Trellakis S, Bruderek K, Schmaltz D, Steller G, Elian M, et al. Myeloid-derived suppressor cells in the peripheral blood of cancer patients contain a subset of immature neutrophils with impaired migratory properties. J Leukoc Biol. 2010 [PubMed]
58. Kusmartsev S, Eruslanov E, Kubler H, Tseng T, Sakai Y, Su Z, et al. Oxidative stress regulates expression of VEGFR1 in myeloid cells: link to tumor-induced immune suppression in renal cell carcinoma. J Immunol. 2008;181:346–53. [PubMed]
59. Nefedova Y, Fishman M, Sherman S, Wang X, Beg AA, Gabrilovich DI. Mechanism of All-Trans Retinoic Acid Effect on Tumor-Associated Myeloid-Derived Suppressor Cells. Cancer Res. 2007;67:11021–8. [PubMed]
60. Xin H, Zhang C, Herrmann A, Du Y, Figlin R, Yu H. Sunitinib inhibition of Stat3 induces renal cell carcinoma tumor cell apoptosis and reduces immunosuppressive cells. Cancer Res. 2009;69:2506–13. [PMC free article] [PubMed]
61. Vincent J, Mignot G, Chalmin F, Ladoire S, Bruchard M, Chevriaux A, et al. 5-Fluorouracil selectively kills tumor-associated myeloid-derived suppressor cells resulting in enhanced T cell-dependent antitumor immunity. Cancer Res. 2010;70:3052–61. [PubMed]
62. Serafini P, Mgebroff S, Noonan K, Borrello I. Myeloid-derived suppressor cells promote cross-tolerance in B-cell lymphoma by expanding regulatory T cells. Cancer Res. 2008;68:5439–49. [PMC free article] [PubMed]
63. Rodriguez PC, Hernandez CP, Quiceno D, Dubinett SM, Zabaleta J, Ochoa JB, et al. Arginase I in myeloid suppressor cells is induced by COX-2 in lung carcinoma. J Exp Med. 2005;202:931–9. [PMC free article] [PubMed]
64. Sinha P, Clements VK, Fulton AM, Ostrand-Rosenberg S. Prostaglandin E2 promotes tumor progression by inducing myeloid-derived suppressor cells. Cancer Res. 2007;67:4507–13. [PubMed]
65. Melani C, Sangaletti S, Barazzetta FM, Werb Z, Colombo MP. 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. Cancer Res. 2007;67:11438–46. [PMC free article] [PubMed]
66. Wiers KM, Lathers DM, Wright MA, Young MR. Vitamin D3 treatment to diminish the levels of immune suppressive CD34+ cells increases the effectiveness of adoptive immunotherapy. J Immunother. 2000;23:115–24. [PubMed]
67. Lathers DM, Clark JI, Achille NJ, Young MR. Phase 1B study to improve immune responses in head and neck cancer patients using escalating doses of 25-hydroxyvitamin D3. Cancer Immunol Immunother. 2004;53:422–30. [PubMed]
68. Fricke I, Mirza N, Dupont J, Lockhart C, Jackson A, Lee JH, et al. Vascular endothelial growth factor-trap overcomes defects in dendritic cell differentiation but does not improve antigen-specific immune responses. Clin Cancer Res. 2007;13:4840–8. [PubMed]
69. Nagaraj S, Youn JI, Weber H, Iclozan C, Lu L, Cotter MJ, et al. Anti-inflammatory Triterpenoid Blocks Immune Suppressive Function of MDSCs and Improves Immune Response in Cancer. Clin Cancer Res. 2010 [PMC free article] [PubMed]
70. De Santo C, Serafini P, Marigo I, Dolcetti L, Bolla M, Del Soldato P, et al. Nitroaspirin corrects immune dysfunction in tumor-bearing hosts and promotes tumor eradication by cancer vaccination. Proc Natl Acad Sci U S A. 2005;102:4185–90. [PMC free article] [PubMed]
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