Tumor-Induced Immune Dysfunctions Caused by Myeloid Suppressor Cells

Journal of Immunotherapy

Volumn 24, Issue 6, 2001, Pages 431-446

  Bronte, Vincenzo ^a   Serafini, Paolo ^a   Apolloni, Elisa ^a   Zanovello, Paola ^a  

^a UNIVERSITY HOSPITAL OF PADOVA   (Italy)

Author keywords

Cancer immunotherapy; Immunosuppression; Myeloid cells

Indexed keywords

GRANULOCYTE COLONY STIMULATING FACTOR; GRANULOCYTE MACROPHAGE COLONY STIMULATING FACTOR;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANTIGEN SPECIFICITY; B LYMPHOCYTE; BONE MARROW CELL; CANCER IMMUNOTHERAPY; CELL POPULATION; DENDRITIC CELL; HUMAN; HUMAN CELL; IMMUNE DEFICIENCY; IMMUNE RESPONSE; IMMUNOREACTIVITY; MACROPHAGE; MAJOR HISTOCOMPATIBILITY COMPLEX RESTRICTION; MOUSE; NONHUMAN; PHENOTYPE; PRIORITY JOURNAL; REVIEW; STEM CELL; SUPPRESSOR CELL; T LYMPHOCYTE ACTIVATION; TUMOR IMMUNITY;

ANIMALS; HUMANS; IMMUNE TOLERANCE; MYELOID CELLS; NEOPLASMS; RECEPTORS, INTERLEUKIN-2; SIGNAL TRANSDUCTION;

EID: 0035201127     PISSN: 15249557     EISSN: 15374513     Source Type: Journal    
DOI: 10.1097/00002371-200111000-00001     Document Type: Review

References (131)

1. Strober S. Natural suppressor (NS) cells, neonatal tolerance, and total lymphoid irradiation: exploring obscure relationships. Annu Rev Immunol 1984; 2: 219-37.
2. Maier T, Holda JH, Claman HN. Natural suppressor cells. Prog Clin Biol Res 1989; 288: 235-44.
3. Maier T, Holda JH, Claman HN. Graft-vs-host reactions (GVHR) across minor murine histocompatibility barriers. II. Development of natural suppressor cell activity. J Immunol 1985; 135: 1644-51.
4. Strober S, Dejbachsh-Jones S, Van Vlasselaer P, et al. 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 1989; 143: 1118-22.
5. Pritchard LL, Huchet R, Bruley-Rosset M, et al. Induction and suppression of delayed-type hypersensitivity to non-MHC antigens during lethal graft-versus-host reaction. J Immunol 1992; 149: 45-52.
6. Sykes M, Sharabi Y, Sachs DH. 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 1990; 127: 260-74.
7. May RD, Slavin S, Vitetta ES. A partial characterization of suppressor cells in the spleens of mice conditioned with fractionated total lymphoid irradiation (TLI). J Immunol 1983; 131: 1108-14.
8. Jaffe ML, Arai H, Nabel GJ. Mechanisms of tumor-induced immunosuppression: evidence for contact-dependent T cell suppression by monocytes. Mol Med 1996; 2: 692-701.
9. Fu YX, Watson GA, Kasahara M, et al. The role of tumor-derived cytokines on the immune system of mice bearing a mammary adenocarcinoma. I. Induction of regulatory macrophages in normal mice by the in vivo administration of rGM-CSF. J Immunol 1991; 146: 783-9.
10. Sugiura K, Inaba M, Ogata H, et al. Wheat germ agglutinin-positive cells in a stem cell-enriched fraction of mouse bone marrow have potent natural suppressor activity. Proc Natl Acad Sci USA 1988; 85: 4824-6.
11. Yoshida T, Norihisa Y, Habu S, et al. Proliferation of natural suppressor cells in long-term cultures of spleen cells from normal adult mice. J Immunol 1991; 147: 4136-9.
12. Brooks Kaiser JC, Bourque LA, Hoskin DW. Heterogeneity of splenic natural suppressor cells induced in mice by treatment with cyclophosphamide. Immunopharmacology 1993; 25: 117-29.
13. Harrington NP, Chambers KA, Ross WM, et al. Radiation damage and immune suppression in splenic mononuclear cell populations. Clin Exp Immunol 1997; 107: 417-24.
14. Young MR, Wright MA, Matthews JP, et al. Suppression of T cell proliferation by tumor-induced granulocyte-macrophage progenitor cells producing transforming growth factor-beta and nitric oxide. J Immunol 1996; 156: 1916-22.
15. Oehler JR, Herberman RB, Campbell Jr, DA et al. Inhibition of rat mixed lymphocyte cultures by suppressor macrophages. Cell Immunol 1977; 29: 238-50.
16. Elgert KD, Alleva DG, Mullins DW. Tumor-induced immune dysfunction: the macrophage connection. J Leukocyte Biol 1998; 64: 275-90.
17. Malick AP, Elgert KD, Garner RE, et al. Prostaglandin E2 production by Mac-2+ macrophages: tumor-induced population shift. J Leukocyte Biol 1987; 42: 673-81.
18. Garner RE, Elgert KD. Changes in splenic macrophage Mac antigen expression during tumor growth: a kinetic study of accessory cell function and antigen-defined phenotypes. J Leukocyte Biol 1986; 40: 709-24.
19. Watson GA, Lopez DM. Aberrant antigen presentation by macrophages from tumor-bearing mice is involved in the down-regulation of their T cell responses. J Immunol 1995; 155: 3124-34.
20. McKnight AJ, Gordon S. Membrane molecules as differentiation antigens of murine macrophages. Adv Immunol 1998; 68: 271-314.
21. Mosmann TR, Sad S. The expanding universe of T-cell subsets: Th1, Th2 and more. Immunol Today 1996; 17: 138-46.
22. Doherty TM. T-cell regulation of macrophage function. Curr Opin Immunol 1995; 7: 400-4.
23. Goerdt S, Orfanos CE. Other functions, other genes: alternative activation of antigen-presenting cells. Immunity 1999; 10: 137-42.
24. Stein M, Keshav S, Harris N, et al. Interleukin 4 potently enhances murine macrophage mannose receptor activity: a marker of alternative immunologic macrophage activation. J Exp Med 1992; 176: 287-92.
25. Schebesch C, Kodelja V, Muller C, et al. Alternatively activated macrophages actively inhibit proliferation of peripheral blood lymphocytes and CD4+ T cells in vitro. Immunology 1997; 92: 478-86.
26. Marincola FM, Jaffee EM, Hicklin DJ, et al. Escape of human solid tumors from T-cell recognition: molecular mechanisms and functional significance. Adv Immunol 2000; 74: 181-273.
27. Taniguchi M, Nakayama T. Recognition and function of Valpha14 NKT cells. Semin Immunol 2000; 12: 543-50.
28. Braud VM, Allan DS, McMichael AJ. Functions of nonclassical MHC and non-MHC-encoded class I molecules. Curr Opin Immunol 1999; 11: 100-8.
29. Mach N, Gillessen S, Wilson SB, et al. Differences in dendritic cells stimulated in vivo by tumors engineered to secrete granulocyte-macrophage colony-stimulating factor or Flt3 ligand. Cancer Res 2000; 60: 3239-46.
30. Matsui S, Ahlers JD, Vortmeyer AO, et al. A model for CD8+ CTL tumor immunosurveillance and regulation of tumor escape by CD4 T cells through an effect on quality of CTL. J Immunol 1999; 163: 184-93.
31. Moodycliffe AM, Nghiem D, Clydesdale G, et al. Immune suppression and skin cancer development: regulation by NKT cells. Nat Immunol 2000; 1: 521-5.
32. Fong L, Engleman EG. Dendritic cells in cancer immunotherapy. Annu Rev Immunol 2000; 18: 245-73.
33. Banchereau J, Briere F, Caux C, et al. Immunobiology of dendritic cells. Annu Rev Immunol 2000; 18: 767-811.
34. Dhodapkar MV, Steinman RM, Krasovsky J, et al. Antigen-specific inhibition of effector T cell function in humans after injection of immature dendritic cells. J Exp Med 2001; 193: 233-8.
35. Jonuleit H, Schmitt E, Schuler G, et al. Induction of interleukin 10-producing, nonproliferating CD4(+) T cells with regulatory properties by repetitive stimulation with allogeneic immature human dendritic cells. J Exp Med 2000; 192: 1213-22.
36. Roncarolo MG, Levings MK. The role of different subsets of T regulatory cells in controlling autoimmunity. Curr Opin Immunol 2000; 12: 676-83.
37. Allavena P, Sica A, Vecchi A, et al. The chemokine receptor switch paradigm and dendritic cell migration: its significance in tumor tissues. Immunol Rev 2000; 177: 141-9.
38. Bell D, Chomarat P, Broyles D, et al. in breast carcinoma tissue, immature dendritic cells reside within the tumor, whereas mature dendritic cells are located in peritumoral areas. J Exp Med 1999; 190: 1417-26.
39. Almand B, Resser JR, Lindman B, et al. Clinical significance of defective dendritic cell differentiation in cancer. Clin Cancer Res 2000; 6: 1755-66.
40. Gabrilovich DI, Chen HL, Girgis KR, et al. Production of vascular endothelial growth factor by human tumors inhibits the functional maturation of dendritic cells. Nat Med 1996; 2: 1096-103.
41. Gabrilovich DI, Corak J, Ciernik IF, et al. Decreased antigen presentation by dendritic cells in patients with breast cancer. Clin Cancer Res 1997; 3: 483-90.
42. Bronte V, Wang M, Overwijk WW, 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.
43. Bronte V, Chappel DB, Apolloni E, et al. Unopposed production of granulocyte-macrophage colony-stimulating factor by tumors inhibits CD8+ T cell responses by dysregulating antigen-presenting cell maturation. J Immunol 1999; 162: 5728-37.
44. Bronte V, Apolloni E, Cabrelle A, et al. Identification of a CD11b+/Gr-1+/CD31+ myeloid progenitor capable of activating or suppressing CD8+ T cells. Blood 2000; 96: 3838-46.
45. de Bruijn MF, Slieker WA, van der Loo JC, et al. Distinct mouse bone marrow macrophage precursors identified by differential expression of ER-MP12 and ER-MP20 antigens. Eur J Immunol 1994; 24: 2279-84.
46. Kusmartsev SA, Li Y, Chen SH. Gr-1+ myeloid cells derived from tumor-bearing mice inhibit primary T cell activation induced through CD3/CD28 costimulation. J Immunol 2000; 165: 779-85.
47. Salvadori S, Martinelli G, Zier K. Resection of solid tumors reverses T cell defects and restores protective immunity. J Immunol 2000; 164: 2214-20.
48. Gabrilovich DI, Velders MP, Sotomayor EM, et al. Mechanism of immune dysfunction in cancer mediated by immature gr-1(+) myeloid cells. J Immunol 2001; 166: 5398-406.
49. Angulo I, de las Heras FG, Garcia-Bustos JF, et al. Nitric oxide-producing CD11b(+)Ly-6G(Gr-1)(+)CD31(ER-MP12)(+) cells in the spleen of cyclophosphamide-treated mice: implications for T-cell responses in immunosuppressed mice. Blood 2000; 95: 212-20.
50. Pelaez B, Campillo JA, Lopez-Asenjo JA, et al. Cyclophosphamide induces the development of early myeloid cells suppressing tumor cell growth by a nitric oxide-dependent mechanism. J Immunol 2001; 166: 6608-15.
51. Horiguchi S, Petersson M, Nakazawa T, et al. Primary chemically induced tumors induce profound immunosuppression concomitant with apoptosis and alterations in signal transduction in T cells and NK cells. Cancer Res 1999; 59: 2950-6.
52. Cauley LS, Miller EE, Yen M, et al. Superantigen-induced CD4 T cell tolerance mediated by myeloid cells and IFN-gamma. J Immunol 2000; 165: 6056-66.
53. Kuwata T, Wang IM, Tamura T, et al. Vitamin A deficiency in mice causes a systemic expansion of myeloid cells. Blood 2000; 95: 3349-56.
54. Schleifer KW, Mansfield JM. Suppressor macrophages in African trypanosomiasis inhibit T cell proliferative responses by nitric oxide and prostaglandins. J Immunol 1993; 151: 5492-503.
55. al-Ramadi BK, Brodkin MA, Mosser DM, et al. Immunosuppression induced by attenuated Salmonella. Evidence for mediation by macrophage precursors. J Immunol 1991; 146: 2737-46.
56. Pak AS, Wright MA, Matthews JP, et al. 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.
57. Young MR, Wright MA, Lozano Y, et al. 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 1997; 74: 69-74.
58. Garrity T, Pandit R, Wright MA, et al. Increased presence of CD34+ cells in the peripheral blood of head and neck cancer patients and their differentiation into dendritic cells. Int J Cancer 1997; 73: 663-9.
59. Almand B, Clark JI, Nikitina E, et al. Increased production of immature myeloid cells in cancer patients: a mechanism of immunosuppression in cancer. J Immunol 2001; 166: 678-89.
60. Tsuchiya Y, Igarashi M, Suzuki R, et al. Production of colony-stimulating factor by tumor cells and the factor-mediated induction of suppressor cells. J Immunol 1988; 141: 699-708.
61. Young MR, Wright MA, Young ME. Antibodies to colony-stimulating factors block Lewis lung carcinoma cell stimulation of immune-suppressive bone marrow cells. Cancer Immunol Immunother 1991; 33: 146-152.
62. Rokhlin OW, Griebling TL, Karassina NV, et al. Human prostate carcinoma cell lines secrete GM-CSF and express GM-CSF-receptor on their cell surface. Anticancer Res 1996; 16: 557-563.
63. Lahm H, Wyniger J, Hertig S, et al. Secretion of bioactive granulocyte-macrophage colony-stimulating factor by human colorectal carcinoma cells. Cancer Res 1994; 54: 3700-2.
64. Dranoff G, Jaffee E, Lazenby A, et al. Vaccination with irradiated tumor cells engineered to secrete murine granulocyte-macrophage colony-stimulating factor stimulates potent, specific, and long-lasting anti-tumor immunity. Proc Natl Acad Sci USA 1993; 90: 3539-43.
65. Mach N, Dranoff G. Cytokine-secreting tumor cell vaccines. Curr Opin Immunol 2000; 12: 571-5.
66. Olavarria E, Kanfer EJ. Selection and use of chemotherapy with hematopoietic growth factors for mobilization of peripheral blood progenitor cells. Curr Opin Hematol 2000; 7: 191-6.
67. Warren TL, Weiner GJ. Uses of granulocyte-macrophage colony-stimulating factor in vaccine development. Curr Opin Hematol 2000; 7: 168-73.
68. Mellstedt H, Fagerberg J, Frodin JE, et al. Augmentation of the immune response with granulocyte-macrophage colony-stimulating factor and other hematopoietic growth factors. Curr Opin Hematol 1999; 6: 169-75.
69. Ageitos AG, Ino K, Ozerol I, et al. Restoration of T and NK cell function in GM-CSF mobilized stem cell products from breast cancer patients by monocyte depletion. Bone Marrow Transplant 1997; 20: 117-23.
70. Rutella S, Rumi C, Testa U, et al. Inhibition of lymphocyte blastogenic response in healthy donors treated with recombinant human granulocyte colony-stimulating factor (rhG-CSF): possible role of lactoferrin and interleukin-1 receptor antagonist. Bone Marrow Transplant 1997; 20: 355-64.
71. Tanaka J, Mielcarek M, Torok-Storb B. Impaired induction of the CD28-responsive complex in granulocyte colony-stimulating factor mobilized CD4 T cells. Blood 1998; 91: 347-52.
72. Mielcarek M, Graf L, Johnson G, et al. Production of interleukin-10 by granulocyte colony-stimulating factor-mobilized blood products: a mechanism for monocyte-mediated suppression of T-cell proliferation. Blood 1998; 92: 215-22.
73. Volpi I, Perruccio K, Tosti A, et al. Postgrafting administration of granulocyte colony-stimulating factor impairs functional immune recovery in recipients of human leukocyte antigen haplotype-mismatched hematopoietic transplants. Blood 2001; 97: 2514-21.
74. Young MR, Young ME, Wright MA. 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 1990; 46: 245-50.
75. Young MR, Young ME, Wright MA. Stimulation of immune-suppressive bone marrow cells by colony-stimulating factors. Exp Hematol 1990; 18: 806-11.
76. Wing EJ, Magee DM, Pearson AC, et al. Peritoneal macrophages exposed to purified macrophage colony-stimulating factor (M-CSF) suppress mitogen-and antigen-stimulated lymphocyte proliferation. J Immunol 1986; 137: 2768-73.
77. Munn DH, Shafizadeh E, Attwood JT, et al. Inhibition of T cell proliferation by macrophage tryptophan catabolism. J Exp Med 1999; 189: 1363-72.
78. Hwu P, Du MX, Lapointe R, et al. Indoleamine 2,3-dioxygenase production by human dendritic cells results in the inhibition of T cell proliferation. J Immunol 2000; 164: 3596-9.
79. Mellor AL, Munn DH. Tryptophan catabolism and T-cell tolerance: immunosuppression by starvation? Immunol Today 1999; 20: 469-73.
80. Ellis LM, Fidler IJ. Angiogenesis and metastasis. Eur J Cancer 1996; 32A: 2451-60.
81. Gabrilovich D, Ishida T, Oyama T, et al. Vascular endothelial growth factor inhibits the development of dendritic cells and dramatically affects the differentiation of multiple hematopoietic lineages in vivo. Blood 1998; 92: 4150-66.
82. Saito H, Tsujitani S, Ikeguchi M, et al. Relationship between the expression of vascular endothelial growth factor and the density of dendritic cells in gastric adenocarcinoma tissue. Br J Cancer 1998; 78: 1573-7.
83. Oyama T, Ran S, Ishida T, et al. Vascular endothelial growth factor affects dendritic cell maturation through the inhibition of nuclear factor-kappa B activation in hemopoietic progenitor cells. J Immunol 1998; 160: 1224-32.
84. Ohm JE, Shurin MR, Esche C, et al. Effect of vascular endothelial growth factor and FLT3 ligand on dendritic cell generation in vivo. J Immunol 1999; 163: 3260-8.
85. Maraskovsky E, Brasel K, Teepe M, et al. Dramatic increase in the numbers of functionally mature dendritic cells in Flt3 ligand-treated mice: multiple dendritic cell subpopulations identified. J Exp Med 1996; 184: 1953-62.
86. Pulendran B, Banchereau J, Burkeholder S, et al. Flt3-ligand and granulocyte colony-stimulating factor mobilize distinct human dendritic cell subsets in vivo. J Immunol 2000; 165: 566-72.
87. Trinchieri G. Interleukin-12: a cytokine at the interface of inflammation and immunity. Adv Immunol 1998; 70: 83-243.
88. Lasarte JJ, Corrales FJ, Casares N, et al. Different doses of adenoviral vector expressing IL-12 enhance or depress the immune response to a coadministered antigen: the role of nitric oxide. J Immunol 1999; 162: 5270-7.
89. Tarrant TK, Silver PB, Wahlsten JL, et al. Interleukin 12 protects from a T helper type 1-mediated autoimmune disease, experimental autoimmune uveitis, through a mechanism involving interferon gamma, nitric oxide, and apoptosis. J Exp Med 1999; 189: 219-30.
90. Koblish HK, Hunter CA, Wysocka M, et al. Immune suppression by recombinant interleukin (rIL)-12 involves interferon gamma induction of nitric oxide synthase 2 (iNOS) activity: inhibitors of NO generation reveal the extent of rIL-12 vaccine adjuvant effect. J Exp Med 1998; 188: 1603-10.
91. Kiessling R, Wasserman K, Horiguchi S, et al. Tumor-induced immune dysfunction. Cancer Immunol Immunother 1999; 48: 353-62.
92. Pericle F, Kirken RA, Bronte V, et al. Immunocompromised tumor-bearing mice show a selective loss of STAT5a/b expression in T and B lymphocytes. J Immunol 1997; 159: 2580-5.
93. Otsuji M, Kimura Y, Aoe T, et al. Oxidative stress by tumor-derived macrophages suppresses the expression of CD3 zeta chain of T-cell receptor complex and antigen-specific T-cell responses. Proc Natl Acad Sci USA 1996; 93: 13119-24.
94. Whiteside TL. Signaling defects in T lymphocytes of patients with malignancy. Cancer Immunol Immunother 1999; 48: 346-52.
95. Zea AH, Ochoa MT, Ghosh P, et al. Changes in expression of signal transduction proteins in T lymphocytes of patients with leprosy. Infect Immun 1998; 66: 499-504.
96. Pericle F, Pinto L, Hicks S, et al. HIV-1 infection induces a selective reduction in STAT5 protein expression. J Immunol 1998; 160: 28-31.
97. Borkow G, Leng Q, Weisman Z, et al. Chronic immune activation associated with intestinal helminth infections results in impaired signal transduction and anergy. J Clin Invest 2000; 106: 1053-60.
98. Kuper H, Adami HO, Trichopoulos D. Infections as a major preventable cause of human cancer. J Intern Med 2000; 248: 171-83.
99. Kinzler KW, Vogelstein B. Landscaping the cancer terrain. Science 1998; 280: 1036-7.
100. Balkwill F, Mantovani A. Inflammation and cancer: back to Virchow? Lancet 2001; 357: 539-45.
101. Lin EY, Nguyen AV, Russell RG, et al. Colony-stimulating factor 1 promotes progression of mammary tumors to malignancy. J Exp Med 2001; 193: 727-40.
102. Coussens LM, Tinkle CL, Hanahan D, et al. MMP-9 supplied by bone marrow-derived cells contributes to skin carcinogenesis. Cell 2000; 103: 481-90.
103. Mann A, Breuhahn K, Schirmacher P, et al. Up-and down-regulation of granulocyte/macrophage-colony stimulating factor activity in murine skin increase susceptibility to skin carcinogenesis by independent mechanisms. Cancer Res 2001; 61: 2311-9.
104. Radoja S, Rao TD, Hillman D, et al. Mice bearing late-stage tumors have normal functional systemic T cell responses in vitro and in vivo. J Immunol 2000; 164: 2619-28.
105. Moore SC, Theus SA, Barnett JB, et al. Bone marrow natural suppressor cells inhibit the growth of myeloid progenitor cells and the synthesis of colony-stimulating factors. Exp Hematol 1992; 20: 1178-83.
106. Lee MY, Fevold KL, Dorshkind K, et al. in vivo and in vitro suppression of primary B lymphocytopoiesis by tumor-derived and recombinant granulocyte colony-stimulating factor. Blood 1993; 82: 2062-8.
107. Sugiura K, Inaba M, Ogata H, et al. Inhibition of tumor cell proliferation by natural suppressor cells present in murine bone marrow. Cancer Res 1990; 50: 2582-6.
108. Cauley LS, Cauley KA, Shub F, et al. Transferable anergy: superantigen treatment induces CD4+ T cell tolerance that is reversible and requires CD4-CD8-cells and interferon gamma. J Exp Med 1997; 186: 71-81.
109. Bronte V, Tsung K, Rao JB, et al. IL-2 enhances the function of recombinant poxvirus-based vaccines in the treatment of established pulmonary metastases. J Immunol 1995; 154: 5282-92.
110. Bredt DS, Snyder SH. Nitric oxide: a physiologic messenger molecule. Annu Rev Biochem 1994; 63: 175-95.
111. Apolloni E, Bronte V, Mazzoni A, et al. Immortalized myeloid suppressor cells trigger apoptosis in antigen-activated T lymphocytes. J Immunol 2000; 165: 6723-30.
112. Mazzoni A, Bronte V, Apolloni E, et al. Myeloid suppressor lines inhibit T cell responses by a nitric oxide dependent mechanism. J Immunol 2001 (in press).
113. Nelson BH, Willerford DM. Biology of the interleukin-2 receptor. Adv Immunol 1998; 70: 1-81.
114. Bogdan C, Rollinghoff M, Diefenbach A. Reactive oxygen and reactive nitrogen intermediates in innate and specific immunity. Curr Opin Immunol 2000; 12: 64-76.
115. Bogdan C, Rollinghoff M, Diefenbach A. The role of nitric oxide in innate immunity. Immunol Rev 2000; 173: 17-26.
116. Marshall HE, Merchant K, Stamler JS. Nitrosation and oxidation in the regulation of gene expression. FASEB J 2000; 14: 1889-900.
117. Duhe RJ, Evans GA, Erwin RA, et al. Nitric oxide and thiol redox regulation of Janus kinase activity. Proc Natl Acad Sci USA 1998; 95: 126-31.
118. Bingisser RM, Tilbrook PA, Holt PG, et al. Macrophage-derived nitric oxide regulates T cell activation via reversible disruption of the Jak3/STAT5 signaling pathway. J Immunol 1998; 160: 5729-34.
119. Park HS, Huh SH, Kim MS, et al. Nitric oxide negatively regulates c-Jun N-terminal kinase/stress-activated protein kinase by means of S-nitrosylation. Proc Natl Acad Sci USA 2000; 97: 14382-7.
120. delaTorre A, Schroeder RA, Punzalan C, et al. Endotoxin-mediated S-nitrosylation of p50 alters NF-kappa B-dependent gene transcription in ANA-1 murine macrophages. J Immunol 1999; 162: 4101-8.
121. Brito C, Naviliat M, Tiscornia AC, et al. Peroxynitrite inhibits T lymphocyte activation and proliferation by promoting impairment of tyrosine phosphorylation and peroxynitrite-driven apoptotic death. J Immunol 1999; 162: 3356-66.
122. Glockzin S, von Knethen A, Scheffner M, et al. Activation of the cell death program by nitric oxide involves inhibition of the proteasome. J Biol Chem 1999; 274: 19581-6.
123. Angulo I, Rullas J, Campillo JA, et al. Early myeloid cells are high producers of nitric oxide upon CD40 plus IFN-gamma stimulation through a mechanism dependent on endogenous TNF-alpha and IL-1 alpha. Eur J Immunol 2000; 30: 1263-71.
124. Seung LP, Rowley DA, Dubey P, et al. Synergy between T-cell immunity and inhibition of paracrine stimulation causes tumor rejection. Proc Natl Acad Sci USA 1995; 92: 6254-8.
125. Young MR, Lozano Y, Ihm J, et al. 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 1996; 104: 153-61.
126. Young MR, Ihm J, Lozano Y, et al. Treating tumor-bearing mice with vitamin D3 diminishes tumor-induced myelopoiesis and associated immunosuppression, and reduces tumor metastasis and recurrence. Cancer Immunol Immunother 1995; 41: 37-45.
127. Wright MA, Wiers K, Vellody K, et al. Stimulation of immune suppressive CD34+ cells from normal bone marrow by Lewis lung carcinoma tumors. Cancer Immunol Immunother 1998; 46: 253-60.
128. Lutz MB, Suri RM, Niimi M, et al. Immature dendritic cells generated with low doses of GM-CSF in the absence of IL-4 are maturation resistant and prolong allograft survival in vivo. Eur J Immunol 2000; 30: 1813-22.
129. Young MR, Wright MA. Myelopoiesis-associated immune suppressor cells in mice bearing metastatic Lewis lung carcinoma tumors: gamma interferon plus tumor necrosis factor alpha synergistically reduces immune suppressor and tumor growth-promoting activities of bone marrow cells and diminishes tumor recurrence and metastasis. Cancer Res 1992; 52: 6335-40.
130. Pak AS, Ip G, Wright MA, et al. 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 1995; 55: 885-90.
131. Medot-Pirenne M, Heilman MJ, Saxena M, et al. Augmentation of an antitumor CTL response in vivo by inhibition of suppressor macrophage nitric oxide. J Immunol 1999; 163: 5877-82.