• 1
    Bronte, V. and Zanovello, P., Regulation of immune responses by L-arginine metabolism. Nat. Rev. Immunol. 2005. 5: 641654.
  • 2
    Gabrilovich, D. I. and Nagaraj, S., Myeloid-derived suppressor cells as regulators of the immune system. Nat. Rev. Immunol. 2009. 9: 162174.
  • 3
    Rodriguez, P. C. and Ochoa, A. C., Arginine regulation by myeloid derived suppressor cells and tolerance in cancer: mechanisms and therapeutic perspectives. Immunol. Rev. 2008. 222: 180191.
  • 4
    Rodriguez, P. C., Hernandez, C. P., Quiceno, D., Dubinett, S. M., Zabaleta, J., Ochoa, J. B., Gilbert, J. and Ochoa, A. C., Arginase I in myeloid suppressor cells is induced by COX-2 in lung carcinoma. J. Exp. Med. 2005. 202: 931939.
  • 5
    Serafini, P., Mgebroff, S., Noonan, K. and Borrello, I., Myeloid-derived suppressor cells promote cross-tolerance in B-cell lymphoma by expanding regulatory T cells. Cancer Res. 2008. 68: 54395449.
  • 6
    Huang, B., Pan, P. Y., Li, Q., Sato, A. I., Levy, D. E., Bromberg, J., Divino, C. M. and Chen, S. H., 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. 2006. 66: 11231131.
  • 7
    Pan, P. Y., Ma, G., Weber, K. J., Ozao-Choy, J., Wang, G., Yin, B., Divino, C. M. and Chen, S. H., Immune stimulatory receptor CD40 is required for T-cell suppression and T regulatory cell activation mediated by myeloid-derived suppressor cells in cancer. Cancer Res. 2010. 70: 99108.
  • 8
    Yang, L., Huang, J., Ren, X., Gorska, A. E., Chytil, A., Aakre, M., Carbone, D. P. et al., Abrogation of TGF beta signaling in mammary carcinomas recruits Gr-1+CD11b+myeloid cells that promote metastasis. Cancer Cell 2008. 13: 2335.
  • 9
    Li, H., Han, Y., Guo, Q., Zhang, M. and Cao, X., Cancer-expanded myeloid-derived suppressor cells induce anergy of NK cells through membrane-bound TGF-beta 1. J. Immunol. 2009. 182: 240249.
  • 10
    Srivastava, M. K., Sinha, P., Clements, V. K., Rodriguez, P. and Ostrand-Rosenberg, S., Myeloid-derived suppressor cells inhibit T-cell activation by depleting cystine and cysteine. Cancer Res. 2010. 70: 6877.
  • 11
    Hanson, E. M., Clements, V. K., Sinha, P., Ilkovitch, D. and Ostrand-Rosenberg, S., Myeloid-derived suppressor cells down-regulate L-selectin expression on CD4+and CD8+T cells. J. Immunol. 2009. 183: 937944.
  • 12
    Ostrand-Rosenberg, S. and Sinha, P., Myeloid-derived suppressor cells: linking inflammation and cancer. J. Immunol. 2009. 182: 44994506.
  • 13
    Talmadge, J. E., Pathways mediating the expansion and immunosuppressive activity of myeloid-derived suppressor cells and their relevance to cancer therapy. Clin Cancer Res 2007. 13: 52435248.
  • 14
    Ko, J. S., Bukowski, R. M. and Fincke, J. H., Myeloid-derived suppressor cells: a novel therapeutic target. Curr. Oncol. Rep. 2009. 11: 8793.
  • 15
    Yang, L., DeBusk, L., Fukuda, K., Fingleton, B., Green-Jarvis, B., Shyr, Y., Matrisian, L. et al., Expansion of myeloid immune suppressor Gr+CD11b+cells in tumor-bearing host directly promotes tumor angiogenesis. Cancer Cell 2004. 6: 409421.
  • 16
    Priceman, S. J., Sung, J. L., Shaposhnik, Z., Burton, J. B., Torres-Collado, A. X., Moughon, D. L., Johnson, M. et al., Targeting distinct tumor-infiltrating myeloid cells by inhibiting CSF-1 receptor: combating tumor evasion of antiangiogenic therapy. Blood 2010. 115: 14611471.
  • 17
    Shojaei, F., Wu, X., Malik, A. K., Zhong, C., Baldwin, M. E., Schanz, S., Fuh, G. et al., Tumor refractoriness to anti-VEGF treatment is mediated by CD11b(+)Gr1(+) myeloid cells. Nat. Biotechnol. 2007. 25: 911920.
  • 18
    Bronte, V., Wang, M., Overwijk, W., Surman, D., Pericle, F., Rosenberg, S. A. and Restifo, N. P., Apoptotic death of CD8+T lymphocytes after immunization: induction of a suppressive population of Mac-1+/Gr-1+cells. J. Immunol. 1998. 161: 53135320.
  • 19
    Gabrilovich, D., Ishida, T., Oyama, T., Ran, S., Kravtsov, V., Nadaf, S. and Carbone, D. P., Vascular endothelial growth factor inhibits the development of dendritic cells and dramatically affects the differentiation of multiple hematopoietic lineages in vivo. Blood 1998. 92: 41504166.
  • 20
    Almand, B., Clark, J. I., Nikitina, E., English, N. R., Knight, S. C., Carbone, D. P. and Gabrilovich, D. I., Increased production of immature myeloid cells in cancer patients. A mechanism of immunosuppression in cancer. J. Immunol. 2001. 166: 678689.
  • 21
    Zea, A. H., Rodriguez, P. C., Atkins, M. B., Hernandez, C., Signoretti, S., Zabaleta, J., McDermott, D. et al., Arginase-producing myeloid suppressor cells in renal cell carcinoma patients: a mechanism of tumor evasion. Cancer Res. 2005. 65: 30443048.
  • 22
    Schmielau, J. and Finn, O. J., 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: 47564760.
  • 23
    Movahedi, K., Guilliams, M., Van den Bossche, J., Van den Bergh, R., Gysemans, C., Beschin, A., De Baetselier, P. and Van Ginderachter, J. A., Identification of discrete tumor-induced myeloid-derived suppressor cell subpopulations with distinct T-cell suppressive activity. Blood 2008. 111: 42334244.
  • 24
    Youn, J. I., Nagaraj, S., Collazo, M. and Gabrilovich, D. I., Subsets of myeloid-derived suppressor cells in tumor-bearing mice. J. Immunol. 2008. 181: 57915802.
  • 25
    Fleming, T. J., Fleming, M. L. and Malek, T. R., Selective expression of Ly-6G on myeloid lineage cells in mouse bone marrow. RB6-8C5 mAb to granulocyte-differentiation antigen (Gr-1) detects members of the Ly-6 family. J. Immunol. 1993. 151: 23992408.
  • 26
    Sunderkotter, C., Nikolic, T., Dillon, M. J., Van Rooijen, N., Stehling, M., Drevets, D. A. and Leenen, P. J., Subpopulations of mouse blood monocytes differ in maturation stage and inflammatory response. J. Immunol. 2004. 172: 44104417.
  • 27
    Ribechini, E., Leenen, P. J. and Lutz, M. B., Gr-1 antibody induces STAT signaling, macrophage marker expression and abrogation of myeloid-derived suppressor cell activity in BM cells. Eur. J. Immunol. 2009. 39: 35383551.
  • 28
    Dolcetti, L., Peranzoni, E., Ugel, S., Marigo, I., Fernandez Gomez, A., Mesa, C., Geilich, M. et al., Hierarchy of immunosuppressive strength among myeloid-derived suppressor cell subsets is determined by GM-CSF. Eur. J. Immunol. 2010. 40: 2235.
  • 29
    Ko, J. S., Zea, A. H., Rini, B. I., Ireland, J. L., Elson, P., Cohen, P., Golshayan, A. et al., Sunitinib mediates reversal of myeloid-derived suppressor cell accumulation in renal cell carcinoma patients. Clin. Cancer Res. 2009. 15: 21482157.
  • 30
    Rodriguez, P. C., Ernstoff, M. S., Hernandez, C., Atkins, M., Zabaleta, J., Sierra, R. and Ochoa, A. C., Arginase I-producing myeloid-derived suppressor cells in renal cell carcinoma are a subpopulation of activated granulocytes. Cancer Res. 2009. 69: 15531560.
  • 31
    Peranzoni, E., Zilio, S., Marigo, I., Dolcetti, L., Zanovello, P., Mandruzzato, S. and Bronte, V., Myeloid-derived suppressor cell heterogeneity and subset definition. Curr. Opin. Immunol. 2010. 22: 238244.
  • 32
    Ribechini, E., Greifenberg, V., Sandwick, S. and Lutz, M. B., Subsets, expansion and activation of myeloid-derived suppressor cells. Med. Microbiol. Immunol. 2010. 199: 273281.
  • 33
    Gallina, G., Dolcetti, L., Serafini, P., De Santo, C., Marigo, I., Colombo, M. P., Basso, G. et al., Tumors induce a subset of inflammatory monocytes with immunosuppressive activity on CD8+T cells. J. Clin. Invest. 2006. 116: 27772790.
  • 34
    Yang, R., Cai, Z., Zhang, Y., Yutzy, W. H. t., Roby, K. F. and Roden, R. B., CD80 in immune suppression by mouse ovarian carcinoma-associated Gr-1+CD11b+myeloid cells. Cancer Res. 2006. 66: 68076815.
  • 35
    Nagaraj, S., Gupta, K., Pisarev, V., Kinarsky, L., Sherman, S., Kang, L., Herber, D. et al., Altered recognition of antigen is a novel mechanism of CD8+T cell tolerance in cancer. Nat. Med. 2007. 13: 828835.
  • 36
    Nausch, N., Galani, I. E., Schlecker, E. and Cerwenka, A., Mononuclear myeloid-derived “suppressor” cells express RAE-1 and activate natural killer cells. Blood 2008. 112: 40804089.
  • 37
    Monu, N. and Frey, A. B., Suppression of proximal T cell receptor signaling and lytic function in CD8+tumor-infiltrating T cells. Cancer Res. 2007. 67: 1144711454.
  • 38
    Fricke, I., Mirza, N., Dupont, J., Lockhart, G., Jackson, A., Lee, J.-H., Sosman, J. A. and Gabrilovich, D. I., Treatment of cancer patients with VEGF-Trap overcomes defects in DC differentiation but is insufficient to improve antigen-specific immune responses. Clin. Cancer Res. 2007. 13: 48404848.
  • 39
    Zhou, Z., French, D. L., Ma, G., Eisenstein, S., Chen, Y., Divino, C. M., Keller, G. et al., Development and function of myeloid-derived suppressor cells generated from mouse embryonic and hematopoietic stem cells. Stem Cells 2010. 28: 620632.
  • 40
    Greifenberg, V., Ribechini, E., Rossner, S. and Lutz, M. B., Myeloid-derived suppressor cell activation by combined LPS and IFN-gamma treatment impairs DC development. Eur. J. Immunol. 2009. 39: 28652876.
  • 41
    Yamamoto, Y., Ishigaki, H., Ishida, H., Itoh, Y., Noda, Y. and Ogasawara, K., Analysis of splenic Gr-1(int) immature myeloid cells in tumor-bearing mice. Microbiol. Immunol. 2008. 52: 4753.
  • 42
    Hestdal, K., Ruscetti, F., Ihle, J., Jacobsen, S., Dubois, C., Kopp, W., Longo, D. and Keller, J., Characterization and regulation of RB6-8C5 antigen expression on murine bone marrow cells. J. Immunol. 1991. 147: 2228.
  • 43
    Haile, L. A., Gamrekelashvili, J., Manns, M. P., Korangy, F. and Greten, T. F., CD49d is a new marker for distinct myeloid-derived suppressor cell subpopulations in mice. J. Immunol. 2010. 185: 203210.
  • 44
    Geissmann, F., Manz, M. G., Jung, S., Sieweke, M. H., Merad, M. and Ley, K., Development of monocytes, macrophages, and dendritic cells. Science 2010. 327: 656661.
  • 45
    Mantovani, A., Sica, A., Allavena, P., Garlanda, C. and Locati, M., Tumor-associated macrophages and the related myeloid-derived suppressor cells as a paradigm of the diversity of macrophage activation. Hum. Immunol. 2009. 70: 325330.
  • 46
    Sica, A. and Bronte, V., Altered macrophage differentiation and immune dysfunction in tumor development. J. Clin. Invest. 2007. 117: 11551166.
  • 47
    Mantovani, A., Sozzani, S., Locati, M., Allavena, P. and Sica, A., Macrophage polarization: tumor-associated macrophages as a paradigm for polarized M2 mononuclear phagocytes. Trends Immunol. 2002. 23: 549555.
  • 48
    Quinn, M. T. and Gauss, K. A., Structure and regulation of the neutrophil respiratory burst oxidase: comparison with nonphagocyte oxidases. J. Leukoc. Biol. 2004. 76: 760781.
  • 49
    Marigo, I., Bosio, E., Solito, S., Mesa, C., Fernandez, A., Dolcetti, L., Ugel, S. et al., Tumor-induced tolerance and immune suppression depend on the C/EBPbeta transcription factor. Immunity 2010. 32: 790802.
  • 50
    Lechner, M. G., Liebertz, D. J. and Epstein, A. L., Characterization of cytokine-induced myeloid-derived suppressor cells from normal human peripheral blood mononuclear cells. J. Immunol. 2010. 185: 22732284.
  • 51
    Arora, M., Poe, S. L., Oriss, T. B., Krishnamoorthy, N., Yarlagadda, M., Wenzel, S. E., Billiar, T. R. et al., TLR4/MyD88-induced CD11b(+)Gr-1(int)F4/80(+) non-migratory myeloid cells suppress Th2 effector function in the lung. Mucosal Immunol. 2010. 3: 578593.
  • 52
    Li, Q., Pan, P. Y., Gu, P., Xu, D. and Chen, S. H., Role of immature myeloid Gr-1+cells in the development of antitumor immunity. Cancer Res. 2004. 64: 11301139.
  • 53
    Narita, Y., Wakita, D., Ohkur, T., Chamoto, K. and Nishimura, T., Potential differentiation of tumor bearing mouse CD11b+Gr-1+immature myeloid cells into both suppressor macrophages and immunostimulatory dendritic cells. Biomed. Res. 2009. 30: 715.
  • 54
    Kusmartsev, S. and Gabrilovich, D., STAT1 signaling regulates tumor-associated macrophage-mediated T cell deletion. J. Immunol. 2005. 174: 48804891.
  • 55
    Corzo, C. A., Condamine, T., Lu, L., Cotter, M. J., Youn, J.-I., Cheng, P., Cho, H.-I. et al., HIF-1α regulates function and differentiation of myeloid-derived suppressor cells in the tumor microenvironment. J. Exp. Med. 2010. 207: 24392453.
  • 56
    Umemura, N., Saio, M., Suwa, T., Kitoh, Y., Bai, J., Nonaka, K., Ouyang, G. F. et al., Tumor-infiltrating myeloid-derived suppressor cells are pleiotropic-inflamed monocytes/macrophages that bear M1- and M2-type characteristics. J. Leukoc. Biol. 2008. 83: 11361144.