Myeloid-derived suppressor cells in cancer

Tumor Induced Immune Suppression: Mechanisms and Therapeutic Reversal

Volumn , Issue , 2008, Pages 157-195

  Serafini, Paolo ^a   Bronte, Vincenzo ^b  

^a UNIVERSITY OF MIAMI MILLER SCHOOL OF MEDICINE   (United States)

^b VENETO INSTITUTE OF ONCOLOGY IOV IRCCS   (Italy)

Author keywords

[No Author keywords available]

Indexed keywords

EID: 84920107427     PISSN: None     EISSN: None     Source Type: Book    
DOI: 10.1007/978-0-387-69118-3_8     Document Type: Chapter

References (190)

1. Almand, B., Clark, J. I., Nikitina, E., van Beynen, J., English, N. R., Knight, S. C., Carbone, D. P., and Gabrilovich, D. I. (2001). Increased production of immature myeloid cells in cancer patients: a mechanism of immunosuppression in cancer. J Immunol 166(1):678-689.
2. Alvaro, T., Lejeune, M., Camacho, F. I., Salvado, M. T., Sanchez, L., Garcia, J. F., Lopez, C., Jaen, J., Bosch, R., Pons, L. E., Bellas, C., and Piris, M. A. (2006). The presence of STAT1- positive tumor-associated macrophages and their relation to outcome in patients with follicular lymphoma. Haematologica 91(12):1605-1612.
3. Andrew, P. J., and Mayer, B. (1999). Enzymatic function of nitric oxide synthases. Cardiovasc Res 43(3):521-531.
4. Apolloni, E., Bronte, V., Mazzoni, A., Serafini, P., Cabrelle, A., Segal, D. M., Young, H. A., and Zanovello, P. (2000). Immortalized myeloid suppressor cells trigger apoptosis in antigenactivated T lymphocytes. J Immunol 165(12):6723-6730.
5. Bach, E. A., Aguet, M., and Schreiber, R. D. (1997). The IFN gamma receptor: a paradigm for cytokine receptor signaling. Annu Rev Immunol 15:563-591.
6. Baglole, C. J., Ray, D.M., Bernstein, S. H., Feldon, S. E., Smith, T. J., Sime, P. J., and Phipps, R. P. (2006). More than structural cells, fibroblasts create and orchestrate the tumor microenvironment. Immunol Invest 35(3-4):297-325.
7. Baniyash, M. (2004). TCR zeta-chain downregulation: curtailing an excessive inflammatory immune response. Nat Rev Immunol 4(9):675-687.
8. Beatty, G. L., and Paterson, Y. (2000). IFN-gamma can promote tumor evasion of the immune system in vivo by down-regulating cellular levels of an endogenous tumor antigen. J Immunol 165(10):5502-5508.
9. Beck, C., Schreiber, K., Schreiber, H., and Rowley, D. A. (2003). C-kit+ FcR+ myelocytes are increased in cancer and prevent the proliferation of fully cytolytic T cells in the presence of immune serum. Eur J Immunol 33(1):19-28.
10. Becker, C., Fantini, M. C., and Neurath, M. F. (2006). TGF-beta as a T cell regulator in colitis and colon cancer. Cytokine Growth Factor Rev 17(1-2):97-106.
11. Bingisser, R. M., Tilbrook, P. A., Holt, P. G., and Kees, U. R. (1998). Macrophage-derived nitric oxide regulates T cell activation via reversible disruption of the Jak3/STAT5 signaling pathway. J Immunol 160(12):5729-5734.
12. Biswas, S. K., Gangi, L., Paul, S., Schioppa, T., Saccani, A., Sironi, M., Bottazzi, B., Doni, A., Vincenzo, B., Pasqualini, F., Vago, L., Nebuloni, M., Mantovani, A., and Sica, A. (2006). A distinct and unique transcriptional program expressed by tumor-associated macrophages (defective NF-kappaB and enhanced IRF-3/STAT1 activation). Blood 107(5):2112-2122.
13. Bogdan, C. (2001). Nitric oxide and the immune response. Nat Immunol 2(10):907-916.
14. Brabletz, T., Pfeuffer, I., Schorr, E., Siebelt, F., Wirth, T., and Serfling, E. (1993). Transforming growth factor beta and cyclosporin A inhibit the inducible activity of the interleukin-2 gene in T cells through a noncanonical octamer-binding site. Mol Cell Biol 13(2):1155-1162.
15. Briganti, A., Salonia, A., Gallina, A., Sacca, A., Montorsi, P., Rigatti, P., and Montorsi, F. (2005). Drug insight: oral phosphodiesterase type 5 inhibitors for erectile dysfunction. Nat Clin Pract Urol 2(5):239-247.
16. Bromberg, J. (2002). Stat proteins and oncogenesis. J Clin Invest 109(9):1139-1142.
17. Bronte, V., Apolloni, E., Cabrelle, A., Ronca, R., Serafini, P., Zamboni, P., Restifo, N. P., and Zanovello, P. (2000). Identification of a CD11b(+)/Gr-1(+)/CD31(+) myeloid progenitor capable of activating or suppressing CD8(+) T cells. Blood 96(12):3838-3846.
18. Bronte, V., Chappell, D. B., Apolloni, E., Cabrelle, A., Wang, M., Hwu, P., and Restifo, N. P. (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(10):5728-5737.
19. Bronte, V., Kasic, T., Gri, G., Gallana, K., Borsellino, G., Marigo, I., Battistini, L., Iafrate, M., Prayer-Galetti, T., Pagano, F., and Viola, A. (2005). Boosting antitumor responses of T lymphocytes infiltrating human prostate cancers. J ExpMed 201(8):1257-1268.
20. Bronte, V., Serafini, P., De Santo, C., Marigo, I., Tosello, V., Mazzoni, A., Segal, D. M., Staib, C., Lowel, M., Sutter, G., Colombo, M. P., and Zanovello, P. (2003a). IL-4-induced arginase 1 suppresses alloreactive T cells in tumor-bearing mice. J Immunol 170(1):270-278.
21. Bronte, V., Serafini, P., Mazzoni, A., Segal, D. M., and Zanovello, P. (2003b). L-arginine metabolism in myeloid cells controls T-lymphocyte functions. Trends Immunol 24(6):302-306.
22. Bronte, V., Wang, M., Overwijk, W. W., Surman, D. R., Pericle, F., Rosenberg, S. A., and Restifo, N. P. (1998). Apoptotic death of CD8+ T lymphocytes after immunization: induction of a suppressive population of Mac-1+/Gr-1+ cells. J Immunol 161(10):5313-5320.
23. Bronte, V., and Zanovello, P. (2005). Regulation of immune responses by L-arginine metabolism. Nat Rev Immunol 5(8):641-654.
24. Bruch-Gerharz, D., Schnorr, O., Suschek, C., Beck, K. F., Pfeilschifter, J., Ruzicka, T., and Kolb- Bachofen, V. (2003). Arginase 1 overexpression in psoriasis: limitation of inducible nitric oxide synthase activity as a molecular mechanism for keratinocyte hyperproliferation. Am J Pathol 162(1):203-211.
25. Brys, L., Beschin, A., Raes, G., Ghassabeh, G. H., Noel, W., Brandt, J., Brombacher, F., and De Baetselier, P. (2005). Reactive oxygen species and 12/15-lipoxygenase contribute to the antiproliferative capacity of alternatively activated myeloid cells elicited during helminth infection. J Immunol 174(10):6095-6104.
26. Buettner, R., Mora, L. B., and Jove, R. (2002). Activated STAT signaling in human tumors provides novel molecular targets for therapeutic intervention. Clin Cancer Res 8(4):945-954.
27. Champelovier, P., Boucard, N., Levacher, G., Simon, A., Seigneurin, D., and Praloran, V. (2002). Plasminogen- And colony-stimulating factor-1-associated markers in bladder carcinoma: diagnostic value of urokinase plasminogen activator receptor and plasminogen activator inhibitor type-2 using immunocytochemical analysis. Urol Res 30(5):301-309.
28. Chen, M. L., Wang, F. H., Lee, P. K., and Lin, C. M. (2001). Interleukin-10-induced T cell unresponsiveness can be reversed by dendritic cell stimulation. Immunol Lett 75(2):91-96.
29. Cheng, F., Wang, H. W., Cuenca, A., Huang, M., Ghansah, T., Brayer, J., Kerr, W. G., Takeda, K., Akira, S., Schoenberger, S. P., Yu, H., Jove, R., and Sotomayor, E. M. (2003). A critical role for Stat3 signaling in immune tolerance. Immunity 19(3):425-436.
30. Cirillo, C., Montaldo, P., Lanciotti, M., Parodi, M. T., Castagnola, E., and Ponzoni, M. (1988). [Immunosuppressive factors produced by a T cell line derived from acute lymphoblastic leukemia]. Boll Ist Sieroter Milan 67(4):295-308.
31. Colombo, M. P., and Mantovani, A. (2005). Targeting myelomonocytic cells to revert inflammation-dependent cancer promotion. Cancer Res 65(20):9113-9116.
32. Currie, G. A., Gyure, L., and Cifuentes, L. (1979). Microenvironmental arginine depletion by macrophages in vivo. Br J Cancer 39(6):613-620.
33. Cutler, A., and Brombacher, F. (2005). Cytokine therapy. Ann N Y Acad Sci 1056:16-29.
34. Danna, E. A., Sinha, P., Gilbert, M., Clements, V. K., Pulaski, B. A., and Ostrand-Rosenberg, S. (2004). Surgical removal of primary tumor reverses tumor-induced immunosuppression despite the presence of metastatic disease. Cancer Res 64(6):2205-2211.
35. Das, J., Chen, C. H., Yang, L., Cohn, L., Ray, P., and Ray, A. (2001). A critical role for NF-kappa B in GATA3 expression and TH2 differentiation in allergic airway inflammation. Nat Immunol 2(1):45-50.
36. De Palma, M., Venneri, M. A., Galli, R., Sergi Sergi, L., Politi, L. S., Sampaolesi, M., and Naldini, L. (2005). Tie2 identifies a hematopoietic lineage of proangiogenic monocytes required for tumor vessel formation and a mesenchymal population of pericyte progenitors. Cancer Cell 8(3):211-226.
37. De Santo, C., Serafini, P., Marigo, I., Dolcetti, L., Bolla, M., Del Soldato, P., Melani, C., Guiducci, C., Colombo, M. P., Iezzi, M., Musiani, P., Zanovello, P., and Bronte, V. (2005). Nitroaspirin corrects immune dysfunction in tumor-bearing hosts and promotes tumor eradication by cancer vaccination. Proc Natl Acad Sci USA 102(11):4185-4190.
38. De Vita, F., Orditura, M., Galizia, G., Romano, C., Lieto, E., Iodice, P., Tuccillo, C., and Catalano, G. (2000a). Serum interleukin-10 is an independent prognostic factor in advanced solid tumors. Oncol Rep 7(2):357-361.
39. De Vita, F., Orditura, M., Galizia, G., Romano, C., Roscigno, A., Lieto, E., and Catalano, G. (2000b). Serum interleukin-10 levels as a prognostic factor in advanced non-small cell lung cancer patients. Chest 117(2):365-373.
40. Dias, S., Boyd, R., and Balkwill, F. (1998). IL-12 regulates VEGF and MMPs in a murine breast cancer model. Int J Cancer 78(3):361-365.
41. Dolled-Filhart, M., Camp, R. L., Kowalski, D. P., Smith, B. L., and Rimm, D. L. (2003). Tissue microarray analysis of signal transducers and activators of transcription 3 (Stat3) and phospho- Stat3 (Tyr705) in node-negative breast cancer shows nuclear localization is associated with a better prognosis. Clin Cancer Res 9(2):594-600.
42. Dranoff, G. (2002). GM-CSF-based cancer vaccines. Immunol Rev 188:147-154.
43. Dranoff, G. (2003). GM-CSF-secreting melanoma vaccines. Oncogene 22(20):3188-3192.
44. Duhe, R. J., Evans, G. A., Erwin, R. A., Kirken, R. A., Cox, G. W., and Farrar, W. L. (1998). Nitric oxide and thiol redox regulation of Janus kinase activity. Proc Natl Acad Sci USA 95(1): 126-131.
45. Dunn, G. P., Old, L. J., and Schreiber, R. D. (2004). The immunobiology of cancer immunosurveillance and immunoediting. Immunity 21(2):137-148.
46. Finder, J. D., Petrus, J. L., Hamilton, A., Villavicencio, R. T., Pitt, B. R., and Sebti, S. M. (2001). Signal transduction pathways of IL-1beta-mediated iNOS in pulmonary vascular smooth muscle cells. Am J Physiol Lung Cell Mol Physiol 281(4):L816-L823.
47. Fiorucci, S., Santucci, L., Gresele, P., Faccino, R. M., Del Soldato, P., and Morelli, A. (2003). Gastrointestinal safety of NO-aspirin (NCX-4016) in healthy human volunteers: a proof of concept endoscopic study. Gastroenterology 124(3):600-607.
48. Fischer, T. A., Palmetshofer, A., Gambaryan, S., Butt, E., Jassoy, C., Walter, U., Sopper, S., and Lohmann, S. M. (2001). Activation of cGMP-dependent protein kinase Ibeta inhibits interleukin 2 release and proliferation of T cell receptor-stimulated human peripheral T cells. J Biol Chem 276(8):5967-5974.
49. Freeman, B. D., Danner, R. L., Banks, S. M., and Natanson, C. (2001). Safeguarding patients in clinical trials with high mortality rates. Am J Respir Crit Care Med 164(2):190-192.
50. Fu, Y. X., Watson, G., Jimenez, J. J., Wang, Y., and Lopez, D.M. (1990). Expansion of immunoregulatory macrophages by granulocyte-macrophage colony-stimulating factor derived from a murine mammary tumor. Cancer Res 50:227-234.
51. Gabrilovich, D. I. (2004). Mechanisms and functional significance of tumour-induced dendriticcell defects. Nat Rev Immunol 4(12):941-952.
52. Gabrilovich, D. I., Bronte, V., Chen, S. H., Colombo, M. P., Ochoa, A., Ostrand-Rosenberg, S., and Schreiber, H. (2007). The terminology issue for myeloid-derived suppressor cells. Cancer Res 67(1):425; author reply 426.
53. Gabrilovich, D. I., Chen, H. L., Girgis, K. R., Cunningham, H. T., Meny, G. M., Nadaf, S., Kavanaugh, D., and Carbone, D. P. (1996). Production of vascular endothelial growth factor by human tumors inhibits the functional maturation of dendritic cells. Nat Med 2: 1096-1103.
54. Gabrilovich, D. I., Ishida, T., Oyama, T., Ran, S., Kravtsov, V., Nadaf, S., and Carbone, D. P. (1998). Vascular endothelial growth factor inhibits the development of dendritic cells and dramatically affects the differentiation of multiple hematopoietic lineages in vivo. Blood 92(11):4150-4166.
55. Gabrilovich, D. I., Velders, M. P., Sotomayor, E. M., and Kast, W. M. (2001). Mechanism of immune dysfunction in cancer mediated by immature gr-1(+) myeloid cells. J Immunol 166(9):5398-5406.
56. Gallina, G., Dolcetti, L., Serafini, P., Santo, C. D., Marigo, I., Colombo, M. P., Basso, G., Brombacher, F., Borrello, I., Zanovello, P., Bicciato, S., and Bronte, V. (2006). Tumors induce a subset of inflammatory monocytes with immunosuppressive activity on CD8 T cells. J Clin Invest 116(10):2777-2790.
57. Garrity, T., Pandit, R., Wright, M. A., Benefield, J., Keni, S., and Young, M. R. (1997). Increased presence of CD34+ cells in the peripheral blood of head and neck cancer patients and their differentiation into dendritic cells. Int J Cancer 73(5):663-669.
58. Gasparini, G., Longo, R., Sarmiento, R., and Morabito, A. (2003). Inhibitors of cyclo-oxygenase 2: a new class of anticancer agents? Lancet Oncol 4(10):605-615.
59. Gerharz, C. D., Reinecke, P., Schneider, E. M., Schmitz, M., and Gabbert, H. E. (2001). Secretion of GM-CSF and M-CSF by human renal cell carcinomas of different histologic types. Urology 58(5):821-827.
60. Ghiringhelli, F., Puig, P. E., Roux, S., Parcellier, A., Schmitt, E., Solary, E., Kroemer, G., Martin, F., Chauffert, B., and Zitvogel, L. (2005). Tumor cells convert immature myeloid dendritic cells into TGF-beta-secreting cells inducing CD4+CD25+ regulatory T cell proliferation. J Exp Med 202(7):919-929.
61. Gordon, S. (2003). Alternative activation of macrophages. Nat Rev Immunol 3(1):23-35.
62. Gray, M. J., Poljakovic, M., Kepka-Lenhart, D., and Morris, S. M. Jr (2005). Induction of arginase I transcription by IL-4 requires a composite DNA response element for STAT6 and C/EBPbeta. Gene 353(1):98-106.
63. Hanada, T., Kobayashi, T., Chinen, T., Saeki, K., Takaki, H., Koga, K., Minoda, Y., Sanada, T., Yoshioka, T., Mimata, H., Kato, S., and Yoshimura, A. (2006). IFNgamma-dependent, spontaneous development of colorectal carcinomas in SOCS1-deficient mice. J Exp Med 203(6):1391-1397.
64. Haran-Ghera, N., Krautghamer, R., Lapidot, T., Peled, A., Dominguez, M. G., and Stanley, E. R. (1997). Increased circulating colony-stimulating factor-1 (CSF-1) in SJL/J mice with radiationinduced acute myeloid leukemia (AML) is associated with autocrine regulation of AML cells by CSF-1. Blood 89(7):2537-2545.
65. Hayashi, T., Hideshima, T., Akiyama, M., Raje, N., Richardson, P., Chauhan, D., and Anderson, K. C. (2003). Ex vivo induction of multiple myeloma-specific cytotoxic T lymphocytes. Blood 102(4):1435-1442.
66. Heldin, C. H. (2004). Development and possible clinical use of antagonists for PDGF and TGFbeta. Ups J Med Sci 109(3):165-178.
67. Horiguchi, S., Petersson, M., Nakazawa, T., Kanda, M., Zea, A. H., Ochoa, A. C., and Kiessling, R. (1999). Primary chemically induced tumors induce profound immunosuppression concomitant with apoptosis and alterations in signal transduction in T cells and NK cells. Cancer Res 59(12):2950-2956.
68. Hsiao, J. R., Jin, Y. T., Tsai, S. T., Shiau, A. L., Wu, C. L., and Su, W. C. (2003). Constitutive activation of STAT3 and STAT5 is present in the majority of nasopharyngeal carcinoma and correlates with better prognosis. Br J Cancer 89(2):344-349.
69. Huang, B., Pan, P. Y., Li, Q., Sato, A. I., Levy, D. E., Bromberg, J., Divino, C. M., and Chen, S. H. (2006). Gr-1+CD115+ immature myeloid suppressor cells mediate the development of tumorinduced T regulatory cells and T-cell anergy in tumor-bearing host. Cancer Res 66(2): 1123-1131.
70. Jain, R. K. (2005). Normalization of tumor vasculature: an emerging concept in antiangiogenic therapy. Science 307(5706):58-62.
71. Kaplan, M. H., and Grusby, M. J. (1998). Regulation of T helper cell differentiation by STAT molecules. J Leukoc Biol 64(1):2-5.
72. Keegan, A. D., Nelms, K., White, M., Wang, L. M., Pierce, J. H., and Paul, W. E. (1994). An IL-4 receptor region containing an insulin receptor motif is important for IL-4-mediated IRS-1 phosphorylation and cell growth. Cell 76(5):811-820.
73. Kehrl, J. H., Roberts, A. B., Wakefield, L. M., Jakowlew, S., Sporn, M. B., and Fauci, A. S. (1986). Transforming growth factor beta is an important immunomodulatory protein for human B lymphocytes. J Immunol 137(12):3855-3860.
74. Kono, K., Ressing, M. E., Brandt, R.M., Melief, C. J., Potkul, R. K., Andersson, B., Petersson, M., Kast, W. M., and Kiessling, R. (1996a). Decreased expression of signal-transducing zeta chain in peripheral T cells and natural killer cells in patients with cervical cancer. Clin Cancer Res 2(11):1825-1828.
75. Kono, K., Salazar-Onfray, F., Petersson, M., Hansson, J., Masucci, G., Wasserman, K., Nakazawa, T., Anderson, P., and Kiessling, R. (1996b). Hydrogen peroxide secreted by tumorderived macrophages down-modulates signal-transducing zeta molecules and inhibits tumorspecific T cell- And natural killer cell-mediated cytotoxicity. Eur J Immunol 26(6):1308-1313.
76. Kortylewski, M., Kujawski, M., Wang, T., Wei, S., Zhang, S., Pilon-Thomas, S., Niu, G., Kay, H., Mule, J., Kerr, W. G., Jove, R., Pardoll, D., and Yu, H. (2005). Inhibiting Stat3 signaling in the hematopoietic system elicits multicomponent antitumor immunity. Nat Med 11(12): 1314-1321.
77. Kunicka, J. E., Fox, F. E., Seki, H., Oleszak, E. L., and Platsoucas, C. D. (1991). Hybridomaderived human suppressor factors: inhibition of growth of tumor cell lines and effect on cytotoxic cells. Hum Antibodies Hybridomas 2(3):160-169.
78. Kusmartsev, S., Cheng, F., Yu, B., Nefedova, Y., Sotomayor, E., Lush, R., and Gabrilovich, D. (2003). All-trans-retinoic acid eliminates immature myeloid cells from tumor-bearing mice and improves the effect of vaccination. Cancer Res 63(15):4441-4449.
79. Kusmartsev, S., and Gabrilovich, D. I. (2003). Inhibition of myeloid cell differentiation in cancer: the role of reactive oxygen species. J Leukoc Biol 74(2):186-196.
80. Kusmartsev, S., and Gabrilovich, D. I. (2005). STAT1 signaling regulates tumor-associated macrophage-mediated T cell deletion. J Immunol 174(8):4880-4891.
81. Kusmartsev, S., and Gabrilovich, D. I. (2006a). Effect of tumor-derived cytokines and growth factors on differentiation and immune suppressive features of myeloid cells in cancer. Cancer Metastasis Rev 25(3):323-331.
82. Kusmartsev, S., and Gabrilovich, D. I. (2006b). Role of immature myeloid cells in mechanisms of immune evasion in cancer. Cancer Immunol Immunother 55(3):237-245.
83. Kusmartsev, S., Nagaraj, S., and Gabrilovich, D. I. (2005). Tumor-associated CD8+ T cell tolerance induced by bone marrow-derived immature myeloid cells. J Immunol 175(7): 4583-4592.
84. Kusmartsev, S., Nefedova, Y., Yoder, D., and Gabrilovich, D. I. (2004). Antigen-specific inhibition of CD8+ T cell response by immature myeloid cells in cancer is mediated by reactive oxygen species. J Immunol 172(2):989-999.
85. Lan, Y. Y., Wang, Z., Raimondi, G., Wu, W., Colvin, B. L., de Creus, A., and Thomson, A. W. (2006). "Alternatively activated" dendritic cells preferentially secrete IL-10, expand Foxp3+CD4+ T cells, and induce long-term organ allograft survival in combination with CTLA4-Ig. J Immunol 177(9):5868-5877.
86. Lang, R., Patel, D., Morris, J. J., Rutschman, R. L., and Murray, P. J. (2002). Shaping gene expression in activated and resting primary macrophages by IL-10. J Immunol 169(5):2253-2263.
87. Lathers, D. M., Clark, J. I., Achille, N. J., and Young, M. R. (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(5):422-430.
88. Lim, S. H., Worman, C. P., Jewell, A., and Goldstone, A. H. (1991). Production of tumour-derived suppressor factor in patients with acute myeloid leukaemia. Leuk Res 15(4):263-268.
89. Lin, E. Y., Gouon-Evans, V., Nguyen, A. V., and Pollard, J. W. (2002). The macrophage growth factor CSF-1 in mammary gland development and tumor progression. J Mammary Gland Biol Neoplasia 7(2):147-162.
90. Liu, Y., Van Ginderachter, J. A., Brys, L., De Baetselier, P., Raes, G., and Geldhof, A. B. (2003). Nitric oxide-independent CTL suppression during tumor progression: association with arginase-producing (M2) myeloid cells. J Immunol 170(10):5064-5074.
91. Liu, C., Yu, S., Kappes, J., Wang, J., Grizzle, W. E., Zinn, K. R., and Zhang, H. G. (2007). Expansion of spleen myeloid suppressor cells represses NK cell cytotoxicity in tumor bearing host. Blood 109:4336-4342.
92. Luo, Y., Zhou, H., Krueger, J., Kaplan, C., Lee, S. H., Dolman, C., Markowitz, D., Wu, W., Liu, C., Reisfeld, R. A., and Xiang, R. (2006). Targeting tumor-associated macrophages as a novel strategy against breast cancer. J Clin Invest 116(8):2132-2141.
93. MacDonald, K. P., Rowe, V., Clouston, A. D., Welply, J. K., Kuns, R. D., Ferrara, J. L., Thomas, R., and Hill, G. R. (2005). Cytokine expanded myeloid precursors function as regulatory antigenpresenting cells and promote tolerance through IL-10-producing regulatory T cells. J Immunol 174(4):1841-1850.
94. MacMicking, J., Xie, Q. W., and Nathan, C. (1997). Nitric oxide and macrophage function. Annu Rev Immunol 15:323-350.
95. Macphail, S. E., Gibney, C. A., Brooks, B. M., Booth, C. G., Flanagan, B. F., and Coleman, J. W. (2003). Nitric oxide regulation of human peripheral blood mononuclear cells: critical time dependence and selectivity for cytokine versus chemokine expression. J Immunol 171(9): 4809-4815.
96. Mahnke, K., Qian, Y., Knop, J., and Enk, A. H. (2003). Induction of CD4+/CD25+ regulatory T cells by targeting of antigens to immature dendritic cells. Blood 101(12):4862-4869.
97. Maier, T., Holda, J. H., and Claman, H. N. (1985). Graft-vs-host reactions (GVHR) across minor murine histocompatibility barriers. II. Development of natural suppressor cell activity. J Immunol 135:1644-1651.
98. Maier, T., Holda, J. H., and Claman, H. N. (1989). Natural suppressor cells. Prog Clin Biol Res 288:235-244.
99. Mannick, J. B., Hausladen, A., Liu, L., Hess, D. T., Zeng, M., Miao, Q. X., Kane, L. S., Gow, A. J., and Stamler, J. S. (1999). Fas-induced caspase denitrosylation. Science 284(5414):651-654.
100. Mantovani, A., Sica, A., Sozzani, S., Allavena, P., Vecchi, A., and Locati, M. (2004). The chemokine system in diverse forms of macrophage activation and polarization. Trends Immunol 25(12):677-686.
101. Mazzoni, A., Bronte, V., Visintin, A., Spitzer, J. H., Apolloni, E., Serafini, P., Zanovello, P., and Segal, D. M. (2002). Myeloid suppressor lines inhibit T cell responses by an NO-dependent mechanism. J Immunol 168(2):689-695.
102. Melani, C., Chiodoni, C., Forni, G., and Colombo, M. P. (2003). Myeloid cell expansion elicited by the progression of spontaneous mammary carcinomas in c-erbB-2 transgenic BALB/c mice suppresses immune reactivity. Blood 102(6):2138-2145.
103. Mellor, A. L., and Munn, D. H. (2004). IDO expression by dendritic cells: tolerance and tryptophan catabolism. Nat Rev Immunol 4(10):762-774.
104. Mellor, A. L., Munn, D. H., Chandler, P., Keskin, D., Johnson, T., Marshall, B., Jhaver, K., and Baban, B. (2003). Tryptophan catabolism and T cell responses. Adv Exp Med Biol 527: 27-35.
105. Menetrier-Caux, C., Montmain, G., Dieu, M. C., Bain, C., Favrot, M. C., Caux, C., and Blay, J. Y. (1998). Inhibition of the differentiation of dendritic cells from CD34(+) progenitors by tumor cells: role of interleukin-6 and macrophage colony-stimulating factor. Blood 92(12): 4778-4791.
106. Merchav, S., Apte, R. N., Tatarsky, I., and Ber, R. (1987). Effect of plasmacytoma cells on the production of granulocyte-macrophage colony-stimulating activity (GM-CSA) in the spleen of tumor-bearing mice. Exp Hematol 15(9):995-1000.
107. Moore, S. C., Shaw, M. A., and Soderberg, L. S. (1992). Transforming growth factor-beta is the major mediator of natural suppressor cells derived from normal bone marrow. J Leukoc Biol 52(6):596-601.
108. Mora, L. B., Buettner, R., Seigne, J., Diaz, J., Ahmad, N., Garcia, R., Bowman, T., Falcone, R., Fairclough, R., Cantor, A., Muro-Cacho, C., Livingston, S., Karras, J., Pow-Sang, J., and Jove, R. (2002). Constitutive activation of Stat3 in human prostate tumors and cell lines: direct inhibition of Stat3 signaling induces apoptosis of prostate cancer cells. Cancer Res 62(22):6659-6666.
109. Morel, S., Levy, F., Burlet-Schiltz, O., Brasseur, F., Probst-Kepper, M., Peitrequin, A. L., Monsarrat, B., Van Velthoven, R., Cerottini, J. C., Boon, T., Gairin, J. E., and Van den Eynde, B. J. (2000). Processing of some antigens by the standard proteasome but not by the immunoproteasome results in poor presentation by dendritic cells. Immunity 12(1):107-117.
110. Morris, D. R., Kuepfer, C. A., Ellingsworth, L. R., Ogawa, Y., and Rabinovitch, P. S. (1989). Transforming growth factor-beta blocks proliferation but not early mitogenic signaling events in T-lymphocytes. Exp Cell Res 185(2):529-534.
111. Munder, M., Eichmann, K., and Modolell, M. (1998). Alternative metabolic states in murine macrophages reflected by the nitric oxide synthase/arginase balance: competitive regulation by CD4+ T cells correlates with Th1/Th2 phenotype. J Immunol 160(11):5347-5354.
112. Munder, M., Eichmann, K., Moran, J. M., Centeno, F., Soler, G., and Modolell, M. (1999). Th1/Th2-regulated expression of arginase isoforms in murine macrophages and dendritic cells. J Immunol 163(7):3771-3777.
113. Nagpal, J. K., Mishra, R., and Das, B. R. (2002). Activation of Stat-3 as one of the early events in tobacco chewing-mediated oral carcinogenesis. Cancer 94(9):2393-2400.
114. Nefedova, Y., Cheng, P., Gilkes, D., Blaskovich, M., Beg, A. A., Sebti, S.M., and Gabrilovich, D. I. (2005). Activation of dendritic cells via inhibition of Jak2/STAT3 signaling. J Immunol 175(7):4338-4346.
115. Nefedova, Y., Huang, M., Kusmartsev, S., Bhattacharya, R., Cheng, P., Salup, R., Jove, R., and Gabrilovich, D. (2004). Hyperactivation of STAT3 is involved in abnormal differentiation of dendritic cells in cancer. J Immunol 172(1):464-474.
116. Nikitakis, N. G., Siavash, H., and Sauk, J. J. (2004). Targeting the STAT pathway in head and neck cancer: recent advances and future prospects. Curr Cancer Drug Targets 4(8):637-651.
117. Ostrand-Rosenberg, S., Clements, V. K., Terabe, M., Park, J. M., Berzofsky, J. A., and Dissanayake, S. K. (2002). Resistance to metastatic disease in STAT6-deficient mice requires hemopoietic and nonhemopoietic cells and is IFN-gamma dependent. J Immunol 169(10):5796-5804.
118. Otsuji, M., Kimura, Y., Aoe, T., Okamoto, Y., and Saito, T. (1996). Oxidative stress by tumorderived macrophages suppresses the expression of CD3 zeta chain of T-cell receptor complex and antigen-specific T-cell responses. Proc Natl Acad Sci USA 93(23):13119-13124.
119. Pak, A. S., Ip, G., Wright, M. A., and Young, M. R. (1995a). Treating tumor-bearing mice with low-dose gamma-interferon plus tumor necrosis factor alpha to diminish immune suppressive granulocyte-macrophage progenitor cells increases responsiveness to interleukin 2 immunotherapy. Cancer Res 55(4):885-890.
120. Pak, A. S., Wright, M. A., Matthews, J. P., Collins, S. L., Petruzzelli, G. J., and Young, M. R. I. (1995b). Mechanisms of immune suppression in patients with head and neck cancer: presence of CD34(+) cells which suppress immune functions within cancers that secrete granulocytemacrophage colony-stimulating factor. Clin Cancer Res 1(1):95-103.
121. Park, J. M., Terabe, M., van den Broeke, L. T., Donaldson, D. D., and Berzofsky, J. A. (2005). Unmasking immunosurveillance against a syngeneic colon cancer by elimination of CD4+ NKT regulatory cells and IL-13. Int J Cancer 114(1):80-87.
122. Park, S. J., Nakagawa, T., Kitamura, H., Atsumi, T., Kamon, H., Sawa, S., Kamimura, D., Ueda, N., Iwakura, Y., Ishihara, K., Murakami, M., and Hirano, T. (2004). IL-6 regulates in vivo dendritic cell differentiation through STAT3 activation. J Immunol 173(6):3844-3854.
123. Parmiani, G., Castelli, C., Pilla, L., Santinami, M., Colombo, M. P., and Rivoltini, L. (2007). Opposite immune functions of GM-CSF administered as vaccine adjuvant in cancer patients. Ann Oncol 18(2):226-32.
124. Pawelec, G. (2004). Tumour escape: antitumour effectors too much of a good thing? Cancer Immunol Immunother 53(3):262-274.
125. Pegoraro, L., Fierro, M. T., Lusso, P., Giovinazzo, B., Lanino, E., Giovarelli, M., Matera, L., and Foa, R. (1985). A novel leukemia T-cell line (PF-382) with phenotypic and functional features of suppressor lymphocytes. J Natl Cancer Inst 75(2):285-290.
126. Pericle, F., Kirken, R. A., Bronte, V., Sconocchia, G., DaSilva, L., and Segal, D. M. (1997). Immunocompromised tumor-bearing mice show a selective loss of STAT5a/b expression in T and B lymphocytes. J Immunol 159:2580-2585.
127. Pericle, F., Pinto, L., Hicks, S., Kirken, R. A., Sconocchia, G., Rusnak, J., Dolan, M. J., Sherear, G. M., and Segal, D. (1998). HIV-1 infection induces a selective reduction in STAT5 protein expression. J Immunol 160:28-31.
128. Que, L. G., George, S. E., Gotoh, T., Mori, M., and Huang, Y. C. (2002). Effects of arginase isoforms on NO Production by nNOS. Nitric Oxide 6(1):1-8.
129. Rambaldi, A., Wakamiya, N., Vellenga, E., Horiguchi, J., Warren, M. K., Kufe, D., and Griffin, J. D. (1988). Expression of the macrophage colony-stimulating factor and c-fms genes in human acute myeloblastic leukemia cells. J Clin Invest 81(4):1030-1035.
130. Rane, S. G., and Reddy, E. P. (2000). Janus kinases: components of multiple signaling pathways. Oncogene 19(49):5662-5679.
131. Ratta, M., Fagnoni, F., Curti, A., Vescovini, R., Sansoni, P., Oliviero, B., Fogli, M., Ferri, E., Della Cuna, G. R., Tura, S., Baccarani, M., and Lemoli, R.M. (2002). Dendritic cells are functionally defective in multiple myeloma: the role of interleukin-6. Blood 100(1):230-237.
132. Rodriguez, P. C., Hernandez, C. P., Quiceno, D., Dubinett, S. M., Zabaleta, J., Ochoa, J. B., Gilbert, J., and Ochoa, A. C. (2005). Arginase I in myeloid suppressor cells is induced by COX-2 in lung carcinoma. J ExpMed 202(7):931-939.
133. Rodriguez, P. C., Quiceno, D. G., Zabaleta, J., Ortiz, B., Zea, A. H., Piazuelo, M. B., Delgado, A., Correa, P., Brayer, J., Sotomayor, E. M., Antonia, S., Ochoa, J. B., and Ochoa, A. C. (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(16):5839-5849.
134. Rossner, S., Voigtlander, C., Wiethe, C., Hanig, J., Seifarth, C., and Lutz, M. B. (2005). Myeloid dendritic cell precursors generated from bone marrow suppress T cell responses via cell contact and nitric oxide production in vitro. Eur J Immunol 35(12):3533-3544.
135. Ruegg, C., Yilmaz, A., Bieler, G., Bamat, J., Chaubert, P., and Lejeune, F. J. (1998). Evidence for the involvement of endothelial cell integrin alphaVbeta3 in the disruption of the tumor vasculature induced by TNF and IFN-gamma. Nat Med 4(4):408-414.
136. Salvadori, S., Martinelli, G., and Zier, K. (2000). Resection of solid tumors reverses T cell defects and restores protective immunity. J Immunol 164(4):2214-2220.
137. Schmielau, J., and Finn, O. J. (2001). Activated granulocytes and granulocyte-derived hydrogen peroxide are the underlying mechanism of suppression of T-cell function in advanced cancer patients. Cancer Res 61(12):4756-4760.
138. Seliger, B., Hohne, A., Knuth, A., Bernhard, H., Meyer, T., Tampe, R., Momburg, F., and Huber, C. (1996). Analysis of the major histocompatibility complex class I antigen presentation machinery in normal and malignant renal cells: evidence for deficiencies associated with transformation and progression. Cancer Res 56(8):1756-1760.
139. Serafini, P., Borrello, I., and Bronte, V. (2006a). Myeloid suppressor cells in cancer: recruitment, phenotype, properties, and mechanisms of immune suppression. Semin Cancer Biol 16(1): 53-65.
140. Serafini, P., Carbley, R., Noonan, K. A., Tan, G., Bronte, V., and Borrello, I. (2004a). High-dose granulocyte-macrophage colony-stimulating factor-producing vaccines impair the immune response through the recruitment of myeloid suppressor cells. Cancer Res 64(17):6337-6343.
141. Serafini, P., De Santo, C., Marigo, I., Cingarlini, S., Dolcetti, L., Gallina, G., Zanovello, P., and Bronte, V. (2004b). Derangement of immune responses by myeloid suppressor cells. Cancer Immunol Immunother 53(2):64-72.
142. Serafini, P., Meckel, K., Kelso, M., Noonan, K., Califano, J., Koch, W., Dolcetti, L., Bronte, V., and Borrello, I. (2006b). Phosphodiesterase-5 inhibition augments endogenous antitumor immunity by reducing myeloid-derived suppressor cell function. J ExpMed 203(12):2691-2702.
143. Seung, L. P., Rowley, D. A., Dubey, P., and Schreiber, H. (1995). Synergy between T-cell immunity and inhibition of paracrine stimulation causes tumor rejection. Proc Natl Acad Sci USA 92:6254-6258.
144. Sgadari, C., Angiolillo, A. L., and Tosato, G. (1996). Inhibition of angiogenesis by interleukin-12 is mediated by the interferon-inducible protein 10. Blood 87(9):3877-3882.
145. Shankaran, V., Ikeda, H., Bruce, A. T., White, J.M., Swanson, P. E., Old, L. J., and Schreiber, R. D. (2001). IFNgamma and lymphocytes prevent primary tumour development and shape tumour immunogenicity. Nature 410(6832):1107-1111.
146. Sinha, P., Clements, V. K., Miller, S., and Ostrand-Rosenberg, S. (2005a). Tumor immunity: a balancing act between T cell activation, macrophage activation and tumor-induced immune suppression. Cancer Immunol Immunother 54(11):1137-1142.
147. Sinha, P., Clements, V. K., and Ostrand-Rosenberg, S. (2005b). Reduction of myeloid-derived suppressor cells and induction of M1 macrophages facilitate the rejection of established metastatic disease. J Immunol 174(2):636-645.
148. Sinha, P., Clements, V. K., and Ostrand-Rosenberg, S. (2005c). Interleukin-13-regulated M2 macrophages in combination with myeloid suppressor cells block immune surveillance against metastasis. Cancer Res 65(24):11743-11751.
149. Smith, C. W., Chen, Z., Dong, G., Loukinova, E., Pegram, M. Y., Nicholas-Figueroa, L., and Van Waes, C. (1998). The host environment promotes the development of primary and metastatic squamous cell carcinomas that constitutively express proinflammatory cytokines IL-1alpha, IL-6, GM-CSF, and KC. Clin Exp Metastasis 16(7):655-664.
150. Sombroek, C. C., Stam, A. G., Masterson, A. J., Lougheed, S. M., Schakel, M. J., Meijer, C. J., Pinedo, H. M., van den Eertwegh, A. J., Scheper, R. J., and de Gruijl, T. D. (2002). Prostanoids play a major role in the primary tumor-induced inhibition of dendritic cell differentiation. J Immunol 168(9):4333-4343.
151. Steinbrink, K., Graulich, E., Kubsch, S., Knop, J., and Enk, A. H. (2002). CD4(+) and CD8(+) anergic T cells induced by interleukin-10-treated human dendritic cells display antigen-specific suppressor activity. Blood 99(7):2468-2476.
152. Stoeck, M., Miescher, S., MacDonald, H. R., and Von Fliedner, V. (1989). Transforming growth factors beta slow down cell-cycle progression in a murine interleukin-2 dependent T-cell line. J Cell Physiol 141(1):65-73.
153. Strober, S. (1984). Natural suppressor (NS) cells, neonatal tolerance, and total lymphoid irradiation: exploring obscure relationships. Annu Rev Immunol 2:219-237.
154. Strober, S., Dejbachsh-Jones, S., Van Vlasselaer, P., Duwe, G., Salimi, S., and Allison, J. P. (1989). Cloned natural suppressor cell lines express the CD3+CD4-CD8- surface phenotype and the alpha, beta heterodimer of the T cell antigen receptor. J Immunol 143:1118-1122.
155. Subiza, J. L., Vinuela, J. E., Rodriguez, R., Gil, J., Figueredo, M. A., and De La Concha, E. G. (1989). Development of splenic natural suppressor (NS) cells in Ehrlich tumor-bearing mice. 44:307-314.
156. Suzuki, E., Kapoor, V., Jassar, A. S., Kaiser, L. R., and Albelda, S. M. (2005). Gemcitabine selectively eliminates splenic Gr-1+/CD11b+ myeloid suppressor cells in tumor-bearing animals and enhances antitumor immune activity. Clin Cancer Res 11(18):6713-6721.
157. Sykes, M., Sharabi, Y., and Sachs, D. H. (1990). Natural suppressor cells in spleens of irradiated, bone marrow- reconstituted mice and normal bone marrow: lack of Sca-1 expression and enrichment by depletion of Mac1-positive cells. Cell Immunol 127:260-274.
158. Takeda, K., Clausen, B. E., Kaisho, T., Tsujimura, T., Terada, N., Forster, I., and Akira, S. (1999). Enhanced Th1 activity and development of chronic enterocolitis in mice devoid of Stat3 in macrophages and neutrophils. Immunity 10(1):39-49.
159. Takeda, K., Hatakeyama, K., Tsuchiya, Y., Rikiishi, H., Kumagai, K., (1991). A correlation between GM-CSF gene expression and metastases in murine tumors. Int J Cancer 47:413-420.
160. Talmadge, J. E., Hood, K. C., Zobel, L. C., Shafer, L. R., Coles, M., and Toth, B. (2007). Chemoprevention by cyclooxygenase-2 inhibition reduces immature myeloid suppressor cell expansion. Int Immunopharmacol 7(2):140-151.
161. Terabe, M., and Berzofsky, J. A. (2004). Immunoregulatory T cells in tumor immunity. Curr Opin Immunol 16(2):157-162.
162. Terabe, M., Matsui, S., Noben-Trauth, N., Chen, H., Watson, C., Donaldson, D. D., Carbone, D. P., Paul, W. E., and Berzofsky, J. A. (2000). NKT cell-mediated repression of tumor immunosurveillance by IL-13 and the IL-4R-STAT6 pathway. Nat Immunol 1(6):515-520.
163. Terabe, M., Matsui, S., Park, J. M., Mamura, M., Noben-Trauth, N., Donaldson, D. D., Chen, W., Wahl, S. M., Ledbetter, S., Pratt, B., Letterio, J. J., Paul, W. E., and Berzofsky, J. A. (2003). Transforming growth factor-beta production and myeloid cells are an effector mechanism through which CD1d-restricted T cells block cytotoxic T lymphocyte-mediated tumor immunosurveillance: abrogation prevents tumor recurrence. J Exp Med 198(11): 1741-1752.
164. Terabe, M., Park, J. M., and Berzofsky, J. A. (2004). Role of IL-13 in regulation of anti-tumor immunity and tumor growth. Cancer Immunol Immunother 53(2):79-85.
165. Toi, M., Kondo, S., Suzuki, H., Yamamoto, Y., Inada, K., Imazawa, T., Taniguchi, T., and Tominaga, T. (1996). Quantitative analysis of vascular endothelial growth factor in primary breast cancer. Cancer 77(6):1101-1106.
166. Trikha, M., Corringham, R., Klein, B., and Rossi, J. F. (2003). Targeted anti-interleukin-6 monoclonal antibody therapy for cancer: a review of the rationale and clinical evidence. Clin Cancer Res 9(13):4653-4665.
167. Tsai, P., Weaver, J., Cao, G. L., Pou, S., Roman, L. J., Starkov, A. A., and Rosen, G. M. (2005). L-arginine regulates neuronal nitric oxide synthase production of superoxide and hydrogen peroxide. Biochem Pharmacol 69(6):971-979.
168. Van Ginderachter, J. A., Meerschaut, S., Liu, Y., Brys, L., De Groeve, K., Hassanzadeh Ghassabeh, G., Raes, G., and De Baetselier, P. (2006). Peroxisome proliferator-activated receptor gamma (PPARgamma) ligands reverse CTL suppression by alternatively activated (M2) macrophages in cancer. Blood 108(2):525-535.
169. Wang, S., Yang, J., Qian, J., Wezeman, M., Kwak, L. W., and Yi, Q. (2006). Tumor evasion of the immune system: inhibiting p38 MAPK signaling restores the function of dendritic cells in multiple myeloma. Blood 107(6):2432-2439.
170. Wang, T., Niu, G., Kortylewski, M., Burdelya, L., Shain, K., Zhang, S., Bhattacharya, R., Gabrilovich, D., Heller, R., Coppola, D., Dalton, W., Jove, R., Pardoll, D., and Yu, H. (2004). Regulation of the innate and adaptive immune responses by Stat-3 signaling in tumor cells. Nat Med 10(1):48-54.
171. Wing, E. J., Magee, D. M., Pearson, A. C., Waheed, A., and Shadduck, R. K. (1986). Peritoneal macrophages exposed to purified macrophage colony-stimulating factor (M-CSF) suppress mitogen- And antigen-stimulated lymphocyte proliferation. J Immunol 137(9):2768-2773.
172. Wolfraim, L. A., Walz, T. M., James, Z., Fernandez, T., and Letterio, J. J. (2004). p21Cip1 and p27Kip1 act in synergy to alter the sensitivity of naive T cells to TGF-beta-mediated G1 arrest through modulation of IL-2 responsiveness. J Immunol 173(5):3093-3102.
173. Wu, G., and Morris, S. M. Jr. (1998). Arginine metabolism:nitric oxide and beyond. Biochem J 336(Pt 1):1-17.
174. Xia, Y., Roman, L. J., Masters, B. S., and Zweier, J. L. (1998). Inducible nitric-oxide synthase generates superoxide from the reductase domain. J Biol Chem 273(35):22635-22639.
175. Xia, Y., and Zweier, J. L. (1997). Superoxide and peroxynitrite generation from inducible nitric oxide synthase in macrophages. Proc Natl Acad Sci USA 94(13):6954-6958.
176. Yang, L., DeBusk, L. M., Fukuda, K., Fingleton, B., Green-Jarvis, B., Shyr, Y., Matrisian, L. M., Carbone, D. P., and Lin, P. C. (2004). Expansion of myeloid immune suppressor Gr+CD11b+ cells in tumor-bearing host directly promotes tumor angiogenesis. Cancer Cell 6(4): 409-421.
177. Yang, L., Yamagata, N., Yadav, R., Brandon, S., Courtney, R. L., Morrow, J. D., Shyr, Y., Boothby, M., Joyce, S., Carbone, D. P., and Breyer, R. M. (2003). Cancer-associated immunodeficiency and dendritic cell abnormalities mediated by the prostaglandin EP2 receptor. J Clin Invest 111(5):727-735.
178. Yang, R., Cai, Z., Zhang, Y., Yutzy, W. H. I. V., Roby, K. F., and Roden, R. B. S. (2006). CD80 in immune suppression by mouse ovarian carcinoma-associated Gr-1+CD11b+ myeloid cells. Cancer Res 66(13):6807-6815.
179. Yoshimura, A. (2006). Signal transduction of inflammatory cytokines and tumor development. Cancer Sci 97(6):439-447.
180. Young, M. R., and Cigal, M. (2006). Tumor skewing of CD34+ cell differentiation from a dendritic cell pathway into endothelial cells. Cancer Immunol Immunother 55(5):558-568.
181. Young, M. R., Lozano, Y., Ihm, J., Wright, M. A., and Prechel, M.M. (1996). Vitamin D3 treatment of tumor bearers can stimulate immune competence and reduce tumor growth when treatment coincides with a heightened presence of natural suppressor cells. Cancer Lett 104:153-161.
182. Young, M. R., Wright, M. A., Coogan, M., Young, M. E., and Bagash, J. (1992). Tumor-derived cytokines induce bone marrow suppressor cells that mediate immunosuppression through transforming growth factor beta. Cancer Immunol Immunother 35(1):14-18.
183. Young, M. R., Wright, M. A., Lozano, Y., Prechel, M. M., Benefield, J., Leonetti, J. P., Collins, S. L., and Petruzzelli, G. J. (1997). Increased recurrence and metastasis in patients whose primary head and neck squamous cell carcinomas secreted granulocyte-macrophage colony-stimulating factor and contained CD34+ natural suppressor cells. Int J Cancer 74(1):69-74.
184. Young, M. R., Wright, M. A., and Young, M. E. (1991). Antibodies to colony-stimulating factors block Lewis lung carcinoma cell stimulation of immune-suppressive bone marrow cells. Cancer Immunol Immunother 33:146-152.
185. Young, M. R., Young, M. E., and Wright, M. A. (1990a). Myelopoiesis-associated suppressor-cell activity in mice with Lewis lung carcinoma tumors: interferon-gamma plus tumor necrosis factor-alpha synergistically reduce suppressor cell activity. Int J Cancer 46(2):245-250.
186. Young, M. R., Young, M. E., and Wright, M. A. (1990b). Stimulation of immune-suppressive bone marrow cells by colony- stimulating factors. Exp Hematol 18(7):806-811.
187. Yu, X., Kennedy, R. H., and Liu, S. J. (2003). JAK2/STAT3, not ERK1/2, mediates interleukin- 6-induced activation of inducible nitric-oxide synthase and decrease in contractility of adult ventricular myocytes. J Biol Chem 278(18):16304-16309.
188. Yu, Z., Zhang, W., and Kone, B. C. (2002). Signal transducers and activators of transcription 3 (STAT3) inhibits transcription of the inducible nitric oxide synthase gene by interacting with nuclear factor kappaB. Biochem J 367(Pt 1):97-105.
189. Zea, A. H., Rodriguez, P. C., Atkins, M. B., Hernandez, C., Signoretti, S., Zabaleta, J., McDermott, D., Quiceno, D., Youmans, A., O'Neill, A., Mier, J., and Ochoa, A. C. (2005). Arginase-producing myeloid suppressor cells in renal cell carcinoma patients: a mechanism of tumor evasion. Cancer Res 65(8):3044-3048.
190. Zhang, B., Bowerman, N. A., Salama, J. K., Schmidt, H., Spiotto, M. T., Schietinger, A., Yu, P., Fu, Y. X., Weichselbaum, R. R., Rowley, D. A., Kranz, D.M., and Schreiber, H. (2007). Induced sensitization of tumor stroma leads to eradication of established cancer by T cells. J Exp Med 204(1):49-55.