Skip to main content
SpringerLink
Log in

The immunobiological effects of interleukin-2 in vivo

  • Review
  • Immunotherapy, T Cell Activation, Capillary Leak Syndrome, Cytokines, Adhesion
  • Published:
Cancer Immunology, Immunotherapy Aims and scope Submit manuscript

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

References

  1. Alexander JP, Kudoh S, Melsop KA, Hamilton TA, Edinger MG, Tubbs RR, Sica D, Tuason L, Klein E, Bukowski RM, Finke JH (1993) T-cells infiltrating renal cell carcinoma display a poor proliferative response even though they can produce interleukin 2 and express interleukin 2 receptors. Cancer Res 53: 1380–1387

    PubMed  Google Scholar 

  2. Atzpodien J, Körfer A, Franks CR, Poliwoda H, Kirchner H (1990) Home therapy with recombinant interleukin-2 and interferon-α2b in advanced human malignancies. Lancet 335: 1509–1512

    PubMed  Google Scholar 

  3. Azuma M, Cayabyab M, Phillips JH, Lanier LL (1993) Requirements for CD28-dependent T cell-mediated cytotoxicity. J Immunol 150: 2091–2101

    PubMed  Google Scholar 

  4. Baars JW, Hack CE, Wagstaff J, Eerenberg-Belmer AJM, Wolbink GJ, Thijs LG, Strack van Schijndel RJM, Vall HLJA van der, Pinedo HM (1992) The activation of polymorphonuclear neutrophils and the complement system during immunotherapy with recombinant interleukin-2. Br J Cancer 65: 96–101

    PubMed  Google Scholar 

  5. Balch CM, Riley LB, Bae YJ, Salmeron MA, Platsoucas CD, Eschenbach A von, Itoh K (1990) Patterns of human tumor-infiltrating lymphocytes in 120 human cancers. Arch Surg 125: 200–205

    PubMed  Google Scholar 

  6. Basse P, Herberman RB, Nannmark U, Johansson BR, Hokland M, Wasserman K, Goldfarb RH (1991) Accumulation of adoptively transferred adherent, lymphokine-activated killer cells in murine metastases. J Exp Med 174: 479–488

    PubMed  Google Scholar 

  7. Belldegrun A, Muul LM, Rosenberg SA (1988) Interleukin 2 expanded tumor-infiltrating lymphocytes in human renal cell cancer: Isolation, characterization, and antitumor activity. Cancer Res 48: 206–214

    PubMed  Google Scholar 

  8. Blay J-Y, Favrot MC, Negrier S, Combaret V, Chouaib S, Mercatello A, Kaemmerlen P, Franks CR, Philip T (1990) Correlation between clinical response to interleukin 2 therapy and sustained production of tumor necrosis factor. Cancer Res 50: 2371–2374

    PubMed  Google Scholar 

  9. Bloemena E, Gall H, Ransom JH, Pomato N, Murray JH, Bos E, Scheper RJ, Meijer CJLM, Hanna MG Jr, Vermorken JB (1993) Delayed type hypersensitivity reactions to tumour-associated antigens in colon carcinoma patients immunized with an autologous tumor cell bacillus Calmette-Guérin vaccine. Cancer Res 53: 456–459

    PubMed  Google Scholar 

  10. Boccoli G, Masciulli R, Ruggeri EM, Carlini P, Giannella G, Montesoro E, Mastroberardino G, Isacchi G, Testa U, Calabresi F, Peschle C (1990) Adoptive immunotherapy of human cancer: the cytokine cascade and monocyte activation following high-dose interleukin 2 bolus treatment. Cancer Res 50: 5795–5800

    PubMed  Google Scholar 

  11. Boon T (1993) Teaching the immune system to fight cancer. Sci Am March: 32–39

  12. Braakman E, Goedegebuure PS, Vreugdenhil RJ, Segal DM, Shaw S, Bolhuis RLH (1990) ICAM-melanoma cells are relatively resistant to CD3-mediated T-cell lysis. Int J Cancer 46: 475–480

    PubMed  Google Scholar 

  13. Briscoe DM, Cotran RS, Pober JS (1992) Effects of tumor necrosis factor, lipopolysaccharide, and IL-4 on the expression of vascular cell adhesion molecule-1 in vivo. Correlation with CD3+ T cell infiltration. J Immunol 149: 2954–2960

    PubMed  Google Scholar 

  14. Buckle A-M, Hogg N (1990) Human memory T cells express intercellular adhesion molecule-1 which can be increased by interleukin 2 and interferon-τ. Eur J Immunol 20: 337–341

    PubMed  Google Scholar 

  15. Buter J, Janssen RAJ, Martens A, Sleijfer DTh, De Leij L, Mulder NH (1993) Phase I/II study of low dose intravenous OKT3 and subcutaneous interleukin-2 in metastatic cancer. Eur J Cancer 29A: 2108–2113

    PubMed  Google Scholar 

  16. Chen L, Ashe S, Brady WA, Hellström KE, Ledbetter JA, McGowna P, Linsley PS (1992) Constimulation of antitumor immunity by the B7 counterreceptor for the T lymphocyte molecules CD28 and CTLA-4. Cell 71: 1093–1102

    PubMed  Google Scholar 

  17. Clark JW, Smith JW, Steis RG, Urba WJ, Crum E, Miller R, McKnight J, Beman J, Stevenson HC, Creekmore S, Stewart M, Conlon D, Sznol M, Kremers P, Cohen P, Longo DL (1990) Interleukin 2 and lymphokine-activated killer cell therapy: analysis of a bolus interleukin 2 and a continuous infusion interleukin 2 regimen. Cancer Res 50: 7343–7350

    PubMed  Google Scholar 

  18. Cohen PJ, Lotze MT, Roberts JR, Rosenberg SA, Jaffe ES (1987) The immunopathology of sequential tumor biopsies in patients treated with interleukin-2. Correlation of response with T-cell infiltration and HLA-DR expression. Am J Pathol 129: 208–216

    PubMed  Google Scholar 

  19. Colombo MP, Forni G (1994) Cytokine gene transfer in tumor inhibition and tumor therapy: where are we now? Immunol Today 15: 48–51

    PubMed  Google Scholar 

  20. Cotran RS, Pober JS, Gimbrone MA Jr, Springer TA, Wiebke EA, Gaspari AA, Rosenberg SA, Lotze MT (1987) Endothelial activation during interleukin 2 immunotherapy. A possible mechanism for the vascular leak syndrome. J Immunol 139: 1883–1888

    Google Scholar 

  21. Curti BD, Longo DL, Ochoa AC, Conlon KC, Smith JW II., Alvord WG, Creekmore SP, Fenton RG, Gause BL, Holmlund J, Janik JE, Ochoa J, Rice PA, Sharfman WH, Sznol M, Urba WJ (1993) Treatment of cancer patients with ex vivo anti-CD3-activated killer cells and interleukin-2. J Clin Oncol 11: 652–660

    PubMed  Google Scholar 

  22. Darrow TL, Slingluff CL Jr, Seigler HF (1989) The role of HLA class I antigens in recognition of melanoma cells by tumor-specific cytotoxic T lymphocytes. Evidence for shared tumor antigens. J Immunol 142: 3329–3335

    PubMed  Google Scholar 

  23. Dent LA, Strath M, Mellor AL, Sanderson CJ (1990) Eosinophilia in transgenic mice expressing interleukin 5. J Exp Med 172: 1425–1431

    PubMed  Google Scholar 

  24. Dranoff G, Jaffee E, Lazenby A, Golumbek P, Levitsky H, Brose K, Jackson V, Hamada H, Pardoll D, Mulligan RC (1993) 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 90: 3539–3543

    PubMed  Google Scholar 

  25. Edwards MJ, Abney DL, Heniford BT, Miller FN (1992) Passive immunization against tumor necrosis factor inhibits interleukin-2-induced microvascular alterations and reduces toxicity. Surgery 112: 480–486

    PubMed  Google Scholar 

  26. Ellenhorn JDI, Hirsch R, Schreiber H, Bluestone JA (1988) In vivo administration of anti-CD3 prevents malignant progressor tumor growth. Science 242: 569–571

    PubMed  Google Scholar 

  27. Ellenhorn JD, Woodle ES, Ghobreal I, Thistlethwaite JR, Bluestone JA (1990) Activation of human T cells in vivo following treatment of transplant recipients with OKT3. Transplantation 50: 608–612

    PubMed  Google Scholar 

  28. Ellis TM, Creekmore S, McMannis JD, Braum DP, Harris JA, Fisher RI (1988) Appearance and phenotypic characterization of circulating leu19+cells in cancer patients receiving recombinant interleukin-2. Cancer Res 48: 6597–6602

    PubMed  Google Scholar 

  29. Ettinghausen SE, Puri RK, Rosenberg SA (1988) Increased vascular permeability in organs mediated by the systemic administration of lymphokine-activated killer cells and recombinant interleukin-2 in mice. J Natl Cancer Inst 80: 177–188

    PubMed  Google Scholar 

  30. Fisher B, Packard BS, Read EJ, Carrasquillo JA, Carter CS, Topalian SL, Yang JC, Yolles P, Larson SM, Rosenberg SA (1989) Tumor localization of adoptively transferred indium-111 labeled tumor infiltrating lymphocytes in patients with metastatic melanoma. J Clin Oncol 7: 250–261

    PubMed  Google Scholar 

  31. Foa R, Guarini A, Gansbacher B (1992) IL2 treatment for cancer: from biology to gene therapy. Br J Cancer 66: 992–998

    PubMed  Google Scholar 

  32. Fossat C, Sainty D, Stoppa AM, Blaise D, David M, Maraninchi D, Juhan-Vague I (1993) In vitro inhibition of interleukin-2-induced defective polymorphonuclear chemotaxis by TNF inhibitor. Eur J Haematol 51: 13–17

    PubMed  Google Scholar 

  33. Fraker DL, Langstein HN, Norton JA (1989) Passive immunization against tumor necrosis factor partially abrogates interleukin 2 toxicity. J Exp Med 170: 1015–1020

    PubMed  Google Scholar 

  34. Freedman AS, Freeman GJ, Rhynhart K, Nadler LM (1991) Selective induction of B7/BB-1 on interferon-γ stimulated monocytes: a potential mechanism for amplification of T cell activation through the CD28 pathway. Cell Immunol 137: 429–437

    PubMed  Google Scholar 

  35. Galandrini R, Albi N, Zarcone D, Grossi CE, Velardi A (1992) Adhesion molecule-mediated signals regulate major histocompatibility complex-unrestricted and CD3/T cell receptor-triggered cytotoxicity. Eur J Immunol 22: 2047–2053

    PubMed  Google Scholar 

  36. Griffith KD, Read EJ, Carrasquillo JA, Carter CS, Yang JC, Fisher B, Aebersold P, Packard BS, Yu MY, Rosenberg SA (1989) In vivo distribution of adoptively transferred indium-111-labeled tumor infiltrating lymphocytes and peripheral blood lymphocytes in patients with metastatic melanoma. J Natl Cancer Inst 81: 1709–1717

    PubMed  Google Scholar 

  37. Haelst Pisani C van, Kovach JS, Kita H, Leiferman KM, Gleich GJ, Silver JE, Dennin R, Abrams JS (1991) Administration of interleukin-2 (IL-2) results in increased plasma concentrations of IL-5 and eosinophilia in patients with cancer. Blood 78: 1538–1544

    PubMed  Google Scholar 

  38. Harding FA, Allison JP (1993) CD28-B7 interaction allow the induction of CD8+ cytotoxic T lymphocytes in the absence of exogenous help. J Exp Med 177: 1791–1796

    PubMed  Google Scholar 

  39. Hart DNJ, Starling GC, Calder VL, Fernando NS (1993) B7/BB-1 is a leucocyte differentiation antigen on human dendritic cells induced by activation. Immunology 79: 616–620

    PubMed  Google Scholar 

  40. Herberman RB (1989) Interleukin-2 therapy of human cancer: potential benefits versus toxicity. J Clin Oncol 7: 1–4

    PubMed  Google Scholar 

  41. Herlyn DM, Steplewski Z, Herlyn D, Koprowsky H (1979) Colorectal carcinoma-specific antigen detection by means of monoclonal antibodies. Proc Natl Acad Sci USA 76: 1438–1442

    PubMed  Google Scholar 

  42. Hermann GG, Geertsen PF, Maase H von der, Zeuthen J (1991) Interleukin-2 dose, blood monocyte and CD25+ lymphocyte counts as predictors of clinical response to interleukin-2 therapy in patients with renal cell carcinoma. Cancer Immunol Immunother 34: 111–114

    PubMed  Google Scholar 

  43. Hermann GG, Geertsen PF, Maase H von der, Steven K, Andersen C, Haid T, Zeuthern J (1992) Recombinant interleukin-2 and lymphokine-activated killer cell treatment of advanced bladder cancer: clinical results and immunological effects. Cancer Res 52: 726–733

    PubMed  Google Scholar 

  44. Hibbs JB, Westenfelder C, Taintor R, Vavrin Z, Kablitz C, Baranowski RL, Ward JH, Menlove RL, McMurray MP, Kushner JP, Samlowski WE (1992) Evidence for cytokine-inducible nitric oxide synthesis froml-arginine in patients receiving interleukin-2 therapy. J Clin Invest 89: 867–877

    PubMed  Google Scholar 

  45. Hirsch R, Gress RE, Pluznik DH, Eckhaus M, Bluestone JA (1989) Effects of in vivo administration of anti-CD3 monoclonal antibody on T cell function in mice. II. In vivo activation of T cells. J Immunol 142: 737–743

    PubMed  Google Scholar 

  46. Hirte H, Clark DA (1991) Generation of lymphokine-activated killer cells in human ovarian carcinoma ascitic fluid: identification of transforming growth factor-beta as a suppressive factor. Cancer Immunol Immunother 32: 296–302

    PubMed  Google Scholar 

  47. Hom SS, Rosenberg SA, Topalian SL (1993) Specific immune recognition of autologous tumor by lymphocytes infiltrating colon carcinomas: analysis by cytokine secretion. Cancer Immunol Immunother 36: 1–8

    PubMed  Google Scholar 

  48. Hwu P, Shafer GE, Treisman J, Schindler DG, Gross G, Cowherd R, Rosenberg SA, Eshhar Z (1993) Lysis of ovarian cancer cells by human lymphocytes redirected with a chimeric gene composed of an antibody variable region and the Fc receptor gamma chain. J Exp Med 178: 361–366

    PubMed  Google Scholar 

  49. Itoh K, Platsoucas CD, Balch CM (1988) Autologous tumor-specific cytotoxic T lymphocytes in the infiltrate of human metastatic melanomas. Activation by interleukin 2 and autologous tumor cells, and involvement of the T cell receptor. J Exp Med 168: 1419–1441

    PubMed  Google Scholar 

  50. Itoh K, Balch CM, Murray JL, Parkinson DR, Markowitz AB, Talpaz M, Lee K, Zukiwski AA, Ross MI, Legha SS, et al. (1991) Immunological properties of melanoma tumor-infiltrating lymphocytes before and after IL-2-based biotherapies. In Vivo 5: 647–653

    PubMed  Google Scholar 

  51. Jablons DM, Mulé JJ, McIntosh JK, Sehgal PB, May LT, Huang CM, Rosenberg SA, Lotze MT (1989) IL-6/IFN-β-2 as a circulating hormone. Induction by cytokine administration in humans. J Immunol 142: 1542–1547

    PubMed  Google Scholar 

  52. Jablons D, Bolton E, Mertins S, Rubin M, Pizzo P, Rosenberg SA, Lotze MT (1990) IL-2-based immunotherapy alters circulating neutrophil Fc receptor expression and chemotaxis. J Immunol 144: 3630–3636

    PubMed  Google Scholar 

  53. Jackson AM, Alexandrov AB, Prescott S, James K, Chisholm GD (1992) Expression of adhesion molecules by bladder cancer cells: modulation by interferon-gamma and tumour necrosis factoralpha. J Urol 148: 1583–1586

    PubMed  Google Scholar 

  54. Janssen RAJ, Sleijfer DTh, Heijn AA, Mulder NH, The TH, De Leij L (1992) Peripheral blood lymphocyte number and phenotype prior to therapy correlate with response in subcutaneously applied rIL-2 therapy of renal cell carcinoma. Br J Cancer 66: 1177–1179

    PubMed  Google Scholar 

  55. Janssen R, Jongsma J, Noteboom J, Kroesen BJ, Helfrich W, Kal H, The H, De Leij L (1993) Interleukin-2 enhances T lymphocyte migration to the tumor site. Proc Am Assoc Cancer Res 34: 486

    Google Scholar 

  56. Janssen RAJ, Buter J, Straatsma E, Heijn AA, Sleijfer DTh, De Vries EGE, Mulder NH, The TH, De Leij L (1993) HLA-Dr-expressing CD8bright cells are only temporarily present in the circulation during subcutaneous recombinant interleukin-2 therapy in renal cell carcinoma patients. Cancer Immunol Immunother 36: 198–204

    PubMed  Google Scholar 

  57. Janssen RAJ, Heijn AA, The TH, De Leij L (1994) Poor induction of IL-2R expression on CD8bright cells in whole blood cell cultures with CD3 mAb. Implications for immunotherapy with CD3 mAb. Cancer Immunol Immunother 38: 53–60

    PubMed  Google Scholar 

  58. Jenkins MK (1992) The role of cell division in the induction of clonal anergy. Immunol Today 13: 69–73

    PubMed  Google Scholar 

  59. Kasahara T, Hooks JJ, Dougherty SF, Oppenheim JJ (1983) Interleukin 2-mediated immune interferon (IFN-γ) production by human T cells and T cell subsets. J Immunol 130: 1784–1789

    PubMed  Google Scholar 

  60. Kasid A, Director EP, Rosenberg SA (1989) Induction of endogenous cytokine-mRNA in circulating peripheral blood mononuclear cells by IL-2 administration to cancer patients. J Immunol 143: 736–739

    PubMed  Google Scholar 

  61. Kilbourn RG, Belloni P (1990) Endothelial cell production of nitrogen oxides in response to interferon gamma in combination with tumor necrosis factor, interleukin-1, or endotoxin. J Natl Cancer Inst 82: 772–776

    PubMed  Google Scholar 

  62. Kitayama J, Juju T, Atomi Y, Kuroda A, Muto T, Kobayashi M, Mitsui Y, Minami M (1993) Transendothelial migration activity of lymphokine-activated killer (LAK) cells. J Immunol 151: 1663–1672

    PubMed  Google Scholar 

  63. Klempner MS, Noring R, Mier JW, Atkins MB (1990) An acquired chemotactic defect in neurophils from patients receiving interleukin-2 immunotherapy. N Engl J Med 322: 959–965

    PubMed  Google Scholar 

  64. Knuth A, Wölfel T, Klehmann E, Boon T, Meyer zum Büschenfelde KH (1989) Cytolytic T-cell clones against an autologous human melanoma: specificity study and definition of three antigens by immunoselection. Proc Natl Acad Sci USA 86: 2804–2808

    PubMed  Google Scholar 

  65. Kotasck D, Vercellotti GM, Ochoa AC, Bach FH, White JG, Jacob HS (1988) Mechanism of cultured endothelial injury induced by lymphokine-activated killer cells. Cancer Res 48: 5528–5532

    PubMed  Google Scholar 

  66. Kroesen BJ, Buter J, Sleijfer DTh, Janssen RAJ, Graaf W van der, The TH, De Leij L, Mulder NH (1993) Phase 1 study of intravenously applied bispecific antibody in patients receiving subcutaneous IL-2. Br J Cancer (in press)

  67. Kroesen BJ, ter Haar A, Spakman H, Willemse P, Sleijfer DTh, De Vries EGE, Mulder NH, Berendsen HH, Limburg P, The TH, De Leij L (1993) Local antitumour treatment in carcinoma patients with bispecific monoclonal antibody redirected T-cells. Cancer Immunol Immunother 37: 400–407

    PubMed  Google Scholar 

  68. Lienard D, Ewalenko P, Delmotte J-J, Renard N, Lejeune FJ (1992) High dose recombinant tumor necrosis factor alpha in combination with interferon-gamma and melphalan in isolation perfusion of the limbs for melanoma and sarcoma. J Clin Oncol 10: 52–60

    PubMed  Google Scholar 

  69. Lienard D, Eggermont AMM, Schraffordt Koops H, Lejeune FJ (1993) High dose of rTNFα, rIFNγ and melphalan in isolation perfusion produce 90% complete response in melanoma in transis metastases. In: Fiers W, Buurman WA (eds)Tumor necrosis factor: molecular and cellular biology and clinical relevance. Karger, Basel, pp 233–238

    Google Scholar 

  70. Lotze MT, Matory YL, Rayner AA, Ettinghausen SE, Seipp CA, Rosenberg SA (1986) Clinical effects and toxicity of interleukin-2 in patients with cancer. Cancer 58: 2764–2772

    PubMed  Google Scholar 

  71. Martens A, Janssen RAJ, Sleijfer DTh, Heijn AA, Mulder NH, The TH, De Leij L (1993) Early sCD8 plasma levels during subcutaneous rIL-2 therapy in patients with renal cell carcinoma correlate with response. Br J Cancer 67: 1118–1121

    PubMed  Google Scholar 

  72. McIntyre CA, Chapman K, Reeder S, Dorreen MX, Bruce L, Rodgers S, Hayat K, Schreenivasan T, Sheridan E, Hancock BW, Rees RC (1992) Treatment of malignant melanoma and renal cell carcinoma with recombinant human interleukin-2: analysis of cytokine levels in sera and culture supernatants. Eur J Cancer 28: 58–63

    PubMed  Google Scholar 

  73. Melief CJ, Kast WM (1992) Lessons from T cell responses to virus induced tumours for cancer eradication in general. Cancer Surv 13P: 81–99

    Google Scholar 

  74. Meuer SC, Meyer zum Büschenfelde KH (1986) T cell receptor triggering induces responsiveness to interleukin 1 and interleukin 2 but does not lead to T cell proliferation. J Immunol 136: 4106–4112

    PubMed  Google Scholar 

  75. Mier JW, Brandon EP, Libby P, Janicka MW, Aronson FR (1989) Activated endothelial cells resist lymphokine-activated killer cellmediated injury. Possible role of induced cytokines in limiting capillary leak during IL-2 therapy. J Immunol 143: 2407–2414

    PubMed  Google Scholar 

  76. Mier JW, Vachino G, Klempner MS, Aronson FR, Noring R, Smith S, Brandon EP, Laird W, Atkins MB (1990) Inhibition of interleukin-2-induced tumor necrosis factor release by dexamethasone: prevention of an acquired neutrophil chemotaxis defect and differential suppression of interleukin-2-associated side effects. Blood 10: 1933–1940

    Google Scholar 

  77. Mier JW, Vachino G, Numerof RP, Kotik AN, Atkins MB (1992) Effects of interleukin-2 and interleukin-4 on the synthesis of TNF. Role of TNF in interleukin-2 toxicity. In: Beutler B (ed)Tumor necrosis factors: the molecules and their emerging role in medicine. Raven Press, New York, pp 221–235

    Google Scholar 

  78. Miescher S, Whiteside TL, Carrel S, Fliedner V von (1986) Functional properties of tumor-infiltrating and blood lymphocytes in patients with solid tumors: effects of tumor cells and their supernatants on proliferative responses of lymphocytes. J Immunol 136: 1899–1907

    PubMed  Google Scholar 

  79. Miles DW, Aderka D, Engelmann H, Wallach D, Balkwill FR (1992) Induction of soluble tumour necrosis factor receptors during treatment with interleukin-2. Br J Cancer 66: 1195–1199

    PubMed  Google Scholar 

  80. Mills CD, North RJ (1983) Expression of passively transferred immunity against an established tumor depends on generation of cytolytic T cells in recipient. Inhibition by suppressor T cells. J Exp Med 157: 1448–1460

    PubMed  Google Scholar 

  81. Nagler A, Lanier LL, Cwirla S, Phillips JH (1989) Comparative studies of human FcRIII-positive and negative natural killer cells. J Immunol 143: 3183–3191

    PubMed  Google Scholar 

  82. Nakamura T, Takahashi K, Fukazawa T, Koyanagi M, Yokoyama A, Kato H, Yagita H, Okumura K (1990) Relative contribution of CD2 and LFA-1 to murine T and natural killer cell functions. J Immunol 145: 3628–3624

    PubMed  Google Scholar 

  83. Nitta T, Sato K, Yagita H, Okumura K, Ishii S (1990) Preliminary trial of specific targeting therapy against malignant glioma. Lancet 335: 368–371

    PubMed  Google Scholar 

  84. Ochoa JB, Curti B, Peitzman AB, Simmons RL, Billiar TR, Hoffman R, Rault R, Longo DL, Urba WJ, Ochoa AC (1992) Increased circulating nitrogen oxides after human tumor immunotherapy: correlation with toxic hemodynamic changes. J Natl Cancer Inst 84: 864–867

    PubMed  Google Scholar 

  85. Ohashi Y, Takeshita T, Nagata K, Mori S, Sugamura K (1989) Differential expression of the IL-2 receptor subunits, p55 and p75 on various populations of primary peripheral blood mononuclear cells. J Immunol 143: 3548–3555

    PubMed  Google Scholar 

  86. Olive D, Lopez M, Blaise D, Viens P, Stoppa A-M, Brandely M, Mawas C, Mannoni P, Maraninchi D (1991) Cell surface expression of ICAM-1 (CD54) and LFA-3 (CD58), two adhesion molecules, is up-regulated on bone marrow leukemic blasts after in vivo administration of high-dose recombinant interleukin-2. J Immunother 10: 412–417

    PubMed  Google Scholar 

  87. Pankonin G, Reipert B, Ager A (1992) Interactions between interleukin-2-activated lymphocytes and vascular endothelium: binding to and migration across specialized and non-specialized endothelia. Immunology 77: 51–60

    PubMed  Google Scholar 

  88. Pardi R, Inverardi L, Bender JR (1992) Regulatory mechanisms in leukocyte adhesion: flexible receptors for sophisticated travellers. Immunol Today 13: 224–230.

    PubMed  Google Scholar 

  89. Peace DJ, Cheever MA (1989) Toxicity and therapeutic efficacy of high-dose interleukin 2. J Exp Med 169: 161–173

    PubMed  Google Scholar 

  90. Pober JS, Cotran RS (1992) Immunologic interactions of T lymphocytes with vascular endothelium. Annu Rev Immunol: 261–302

  91. Puri RK, Travis WD, Rosenberg SA (1989) Decrease in interleukin 2-induced vascular leakage in the lungs of mice by administration of recombinant interleukin 1α in vivo. Cancer Res 49: 969–976

    PubMed  Google Scholar 

  92. Rabinowich H, Cohen R, Bruderman I, Steiner Z, Klajman A (1987) Functional analysis of mononuclear cells infiltrating into tumors: lysis of autologous human tumor cells by cultured infiltrating lymphocytes. Cancer Res 47: 173–177

    PubMed  Google Scholar 

  93. Ratner S, Patrick P, Bora G (1992) Lymphocyte development of adherence and motility in extracellular matrix during IL-2 stimulation. J Immunol 149: 681–688

    PubMed  Google Scholar 

  94. Robertson MJ, Caligiuri MA, Manley TJ, Levine H, Ritz J (1990) Human natural killer cell adhesion molecules. Differential expression after activation and participation in cytolysis. J Immunol 145: 3194–3201

    PubMed  Google Scholar 

  95. Rubin JT, Elwood LJ, Rosenberg SA, Lotze MT (1989) Immunohistochemical correlates of response to recombinant interleukin-2 based immunotherapy in humans. Cancer Res 49: 7086–7092

    PubMed  Google Scholar 

  96. Sagone AL Jr, Husney RM, Triozzi PL, Rinehart J (1991) Interleukin-2 therapy enhances salicylate oxidation by blood granulocytes. Blood 78: 2931–2936

    PubMed  Google Scholar 

  97. Salvo G, Samoggia P, Masciaulli R, Boccoli G, Allavena P, Mariani G, Bullo A, Montesoro E, Bulgarini D, Carlini P, Ruggeri EM, Arena MG, Camagna A, Testa U, Calabresi F, Peschle C (1992) Interleukin-2 bolus therapy induces immediate and selective disappearance from peripheral blood of all lymphocyte subpopulations displaying natural killer activity: role of cell adhesion to endothelium. Eur J Cancer 28A: 818–825

    PubMed  Google Scholar 

  98. Schaafsma MR, Falkenburg JH, Landegent JE, Duinkerken N, Osanto S, Ralph P, Kaushansky K, Wagemaker G, Damme J van, Willemze R, Fibbe WE (1991) In vivo production of interleukin-5, granulocyte-macrophage colony-stimulating factor, macrophages colony-stimulating factor, and interleukin-6 during intravenous administration of high-dose interleukin-2 in cancer patients. Blood 78: 1981–1987

    PubMed  Google Scholar 

  99. Schwartz RH (1990) A cell culture model for T lymphocyte clonal anergy. Science 248: 1349–1356

    PubMed  Google Scholar 

  100. Schwartz RH (1992) Constimulation of T lymphocytes: the role of CD28, CTLA-4, and B7/BB1 in interleukin-2 production and immunotherapy. Cell 71: 1065–1068

    PubMed  Google Scholar 

  101. Seventer GA van, Newman W, Shimizu Y, Nutman TB, Tanaka Y, Horgan KJ, Gopal TV, Ennis E, O'Sullivan D, Grey H, Shaw S (1991) Analysis of T cell stimulation by superantigen plus major histocompatibility complex class II molecules or by CD3 monoclonal antibody: costimulation by purified adhesion ligands VCAM-1, ICAM-1, but not ELAM-1. J Exp Med 174: 901–913

    PubMed  Google Scholar 

  102. Shimizu Y, Newman W, Tanaka Y, Shaw S (1992) Lymphocyte interactions with endothelial cells. Immunol Today 13: 106–112

    PubMed  Google Scholar 

  103. Steijfer DTh, Janssen RAJ, Willemse PHB, Martens A, De Leij L, De Vries EGE, Mulder NH (1990) Low-dose regimen of interleukin-2 for metastatic renal carcinoma. Lancet 335: 1522–1523

    Google Scholar 

  104. Sleijfer DTh, Janssen RAJ, Buter J, De Vries EGE, Willemse PHB, Mulder NH (1992) Phase II study of subcutaneous interleukin-2 in unselected patients with advanced renal cell cancer on an outpatient basis. J Clin Oncol 10: 1119–1123

    PubMed  Google Scholar 

  105. Slingluff CL Jr, Darrow TL, Vervaert C, Quinn-Allen MA, Seigler HF (1988) Human cytotoxic T cells specific for autologous melanoma cells: successful generation from lymph node cells in seven consecutive cases. J Natl Cancer Inst 80: 1016–1026

    PubMed  Google Scholar 

  106. Smyth MJ, Strobl SL, Young HA, Ortaldo JR, Ochoa AC (1991) Regulation of lymphokine-activated killer activity and poreforming protein gene expression in human peripheral blood CD8+ T lymphocytes. Inhibition by transforming growth factor-beta. J Immunol 146: 3289–3297

    PubMed  Google Scholar 

  107. Sosman JA, Weiss GR, Margolin KA, Aronson FR, Sznol M, Atkins MB, O'Boyle K, Fisher SG, Mier J, Vachino G, Caliendo G (1993) Phase IB clinical trial of anti-CD3 followed by high-dose bolus interleukin-2 in patients with metastatic melanoma and advanced renal cell carcinoma: clinical and immunologic effects. J Clin Oncol 11: 1496–1505

    PubMed  Google Scholar 

  108. Spiers EM, Potts RC, Sharpe SY, Newman EL, Lavelle-Jones M, Beck JS, Cuschieri A (1993) Response of soluble IL-2 receptor levels to repeated cycles of IL-2 immunotherapy/chemotherapy (letter). Eur J Cancer 29A: 928

    PubMed  Google Scholar 

  109. Steinman RM (1991) The dendritic cell system and its role in immunogenicity. Annu Rev Immunol 9: 271–296

    PubMed  Google Scholar 

  110. Thompson JA, Lee DJ, Lindgren CG? Benz LA, Collins C, Shuman WP, Levitt D, Fefer A (1989) Influence of schedule of interleukin 2 administration on therapy with interleukin 2 and lymphokine activated killer cells. Cancer Res 49: 235–240

    PubMed  Google Scholar 

  111. Tomita Y, Watanabe H, Kobayashi H, Nishiyama T, Tsuji S, Fujiwara M, Sato S (1992) Interferon gamma but not tumor necrosis factor alpha decreases susceptibility of human renal cell cancer cell lines to lymphokine-activated killer cells. Cancer Immunol Immunother 35: 381–387

    PubMed  Google Scholar 

  112. Triozzi PL, Eicher DM, Rinehart JJ (1992) Modulation of adhesion molecules on human large granular lymphocytes by interleukin-2 in vivo and in vitro. Cell Immunol 140: 295–303

    PubMed  Google Scholar 

  113. Tritarelli E, Rocca E, Testa U, Boccoli G, Camagna A, Calabresi F, Peschle C (1991) Adoptive immunotherapy with high-dose interleukin-2: kinetics of circulating progenitors correlate with interleukin-6, granulocyte colony-stimulating factor level. Blood 77: 741–749

    PubMed  Google Scholar 

  114. Umehara H, Bloom ET (1990) The IL-2 receptor beta subunit is absolutely required for mediating the IL-2-induced activation of NK activity and proliferative activity of human large granular lymphocytes. Immunology 70: 111–115

    PubMed  Google Scholar 

  115. Vachino G, Gelfand JA, Atkins MB, Tamcrius JD, Demchak P, Mier JW (1991) Complement activation in cancer patients undergoing immunotherapy with interleukin-2 (IL-2): binding of complement and C-reactive protein by IL-2-activated lymphocytes. Blood 78: 2505–2513

    PubMed  Google Scholar 

  116. Van der Bruggen P, Traversari C, Chomez P, Lurquin C, De Plaen E, Van den Eynde B, Knuth A, Boon T (1991) A gene encoding an antigen recognized by cytolytic T lymphocytes on a human melanoma. Science 254: 1643–1647

    PubMed  Google Scholar 

  117. Velotti F, Stoppacciaro A, Ruco L, Tubaro A, Pettinato A, Morrone S, Napolitano T, Bossola Pc, Franks CR, Palmer P, Pourreau CN, Piccoli M, Baroni CD, Frati L, Miano L, Santoni A (1991) Local activation of immune response in bladder cancer patients treated with intraarterial infusion of recombinant interleukin-2. Cancer Res 51: 2456–2462

    PubMed  Google Scholar 

  118. Virelizier J-L, Perez N, Arenzana-Seisdedos F, Devos R (1984) Pure interferon gamma enhances class II HLA antigens on human monocyte cell lines. Eur J Immunol 14: 106–108

    PubMed  Google Scholar 

  119. Vose B, Vanky F, Klein E (1977) Human tumor-lymphocyte interaction in vitro. V. Comparison of the reactivity of tumor infiltrating blood and lymph node lymphocytes with autologous tumor cells. Int J Cancer 20: 895–902

    PubMed  Google Scholar 

  120. Voss SD, Leary TP, Sondel PM, Robb RJ (1993) Identification of a direct interaction between interleukin 2 and the p64 interleukin 2 receptor γ chain. Proc Natl Acad Sci USA 90: 2428–2432

    PubMed  Google Scholar 

  121. Voss SD, Robb RJ, Weil-Hillman GW, Hank JA, Sugamura K, Tsudo M, Sondel PM (1990) Increased expression of the interleukin 2 (IL-2) receptor B chain (p70) on CD56+ natural killer cells after in vivo IL-2 therapy p70 expression does not alone predict the level of intermediate affinity IL-2 binding. J Exp Med 172: 1101–1114

    PubMed  Google Scholar 

  122. Wallach D, Fellous M, Revel M (1982) Differential effect of μ interferon on the synthesis of HLA antigens and their mRNAs in human cells. Nature 299: 833–836

    PubMed  Google Scholar 

  123. Waal Malefyt R de, Verma S, Bejaramo M-T, Ranes-Goldberg M, Hill M, Spits H (1993) CD2/LFA-3 or LFA-1/ICAM-1 but not CD28/B7 interactions can augment cytotoxicity by virus-specific CD8+ cytotoxic T lymphocytes. Eur J Immunol 23: 418–424

    PubMed  Google Scholar 

  124. Wauwe JP van, Goossens JG, Beverley PCL (1984) Human T lymphocyte activation by monoclonal antibodies: OKT3, but not UCHT1, triggers mitogenesis via an interleukin 2-dependent mechanism. J Immunol 133: 129–132

    PubMed  Google Scholar 

  125. Weil-Hillman G, Fisch P, Prieve AF, Sosman JA, Hank JA, Sondel PM (1989) Lymphokine-activated killer activity induced by in vivo interleukin 2 therapy: predominant role for lymphocytes with increased expression of CD2 and leu 19 antigens but negative expression of CD16 antigens. Cancer Res 49: 3680–3688

    PubMed  Google Scholar 

  126. Weil-Hillman GW, Voss SD, Fisch P, Schell K, Hank JA, Sosman JA, Sugamura K, Sondel PM (1990) Natural killer cells activated by interleukin 2 treatment in vivo respond to interleukin 2 primarily through the p75 receptor and maintain the p55 (TAC) negative phenotype. Cancer Res 50: 2683–2691

    PubMed  Google Scholar 

  127. Weil-Hillman G, Schell K, Segal DM, Hank JA, Sosman JA, Sondel PM (1991) Activation of human T cells obtained pre-and post-interleukin-2 (IL-2) therapy by anti-CD3 monoclonal anti-body plus IL-2, implications for combined in vivo treatment. J Immunother 10: 267–277

    PubMed  Google Scholar 

  128. Weiner LM, Padavic-Shaller K, Kitson J, Watts P, Krigel RL, Litwin S (1991) Phase I evaluation of combination therapy with interleukin 2 and gamma interferon. Cancer Res 51:3910–3918

    PubMed  Google Scholar 

  129. Wiebke EA, Rosenberg SA, Lotze MT (1988) Acute immunologic effects of interleukin-2 therapy in cancer patients: decreased delayed type hypersensitivity response and decreased proliferative response to soluble antigens. J Clin Oncol 6: 1440–1449

    PubMed  Google Scholar 

  130. Yagita H, Nakata M, Azuma A, Nitta T, Takeshita T, Sugamura K, Okumura K (1989) Activation of peripheral blood T cells via the p75 interleukin 2 receptor. J Exp Med 170: 1445–1450

    PubMed  Google Scholar 

  131. Yang SC, Fry KD, Grimm EA, Roth JA (1990) Successful combination immunotherapy for the generation in vivo of antitumor activity with anti-CD3, interleukin 2, and tumor necrosis factor α. Arch Surg 125: 220–225

    PubMed  Google Scholar 

  132. Yang S, Branch C, Grimm EA, Roth JA (1991) Low dose OKT3 prior to IL-2 and TNFα induces and enhances activation of cytotoxic lymphocytes in vivo. Proc Am Assoc Cancer Res 32: 249

    Google Scholar 

  133. Yoshino I, Yano T, Murata M, Ishida T, Sugimachi K, Kimura G, Nomoto K (1991) Cytolytic potential of peripheral blood T lymphocytes following adoptive immunotherapy with lymphokine-activated killer cells and low-dose interleukin 2. Cancer Res 51: 1494–1498

    PubMed  Google Scholar 

  134. Zimmerman GA, Prescott SM, McIntyre TM (1992) Endothelial cell interactions with granulocytes: tethering and signaling molecules. Immunol Today 13: 93–100

    PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Clinical Immunology, University Hospital Groningen, Oostersingel 59, 9713 EZ, Groningen, The Netherlands

    Richard A. J. Janssen, T. Hauw The & Lou de Leij

  2. Department of Medical Oncology, University Hospital Groningen, Oostersingel 59, 9713 EZ, Groningen, The Netherlands

    Nanno H. Mulder

Authors
  1. Richard A. J. Janssen
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Nanno H. Mulder
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. T. Hauw The
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Lou de Leij
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Janssen, R.A.J., Mulder, N.H., Hauw The, T. et al. The immunobiological effects of interleukin-2 in vivo. Cancer Immunol Immunother 39, 207–216 (1994). https://doi.org/10.1007/BF01525983

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF01525983

Key words

Search

Navigation