Skip to main content
SpringerLink
Log in
Book cover

Molecular Basis for Therapy of AIDS-Defining Cancers pp 181–198Cite as

Interferon in Kaposi’s Sarcoma Biology and Therapy

  • Chapter
  • First Online:

Abstract

Interferon alfa (IFN-α) was one of the first drugs shown to have activity against AIDS-associated Kaposi’s sarcoma (KS). Multiple clinical studies have defined IFN-α’s role as a single agent or in combination with antiretroviral drugs against KS and have indicated that preserved immune function and the absence of activation of the endogenous IFN system are markers for improved outcome. Infection with both human immunodeficiency virus (HIV) and the KS-associated herpesvirus (KSHV) has been associated with perturbations in the IFN system, but it is not known precisely how this influences the development of KS, its clinical course, or response to exogenous IFN therapy. Multiple mechanisms have been proposed for IFN-α’s antitumor activity against KS including inhibition of cell proliferation, targeted inhibition of pathways leading to aberrant angiogenesis, and inhibition of both HIV and KSHV, but its precise mechanism of action is not known, nor is it known why some tumors fail to respond. The future development of IFN therapy for KS should include combinations of IFN with other agents and/or the use of IFN preparations that require less frequent administration.

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

Chapter
USD   29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD   169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD   169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Learn about institutional subscriptions

References

  • Albini, A., Soldi, R., Giunciuglio, D., et al. (1996). The angiogenesis induced by HIV-1 tat protein is mediated by the Flk-1/KDR receptor on vascular endothelial cells. Nat Med 2, 1371–1375.

    Article  PubMed  CAS  Google Scholar 

  • Bailey, J., Pluda, J. M., Foli, A., Saville, M. W., et al. (1995). Phase I/II study of intermittent all-trans-retinoic acid, alone and in combination with interferon alfa-2a, in patients with epidemic Kaposi’s sarcoma. J Clin Oncol 13, 1966–1974.

    PubMed  CAS  Google Scholar 

  • Baumann, R., Täuber, M. G., Opravil, M., et al. (1991). Combined treatment with zidovudine and lymphoblast interferon-alpha in patients with HIV-related Kaposi’s sarcoma. Klin Wochenschr 69, 360–367.

    Article  PubMed  CAS  Google Scholar 

  • Blackbourn, D., Fujimura, S., Kutzkey, T., and Levy, J. A. (2000). Induction of human herpesvirus-8 gene expression by recombinant interferon gamma. AIDS 14, 98–99.

    Article  PubMed  CAS  Google Scholar 

  • Brander, C., Suscovich, T., Lee, Y., et al. (2000). Impaired CTL recognition of cells latently infected with Kaposi’s sarcoma-associated herpes virus. J Immunol 165, 2077–2083.

    PubMed  CAS  Google Scholar 

  • Buimovici-Klein, E., Lange, M., Klein, R. J., Cooper, L. Z., and Grieco, M. H. (1983). Is presence of interferon predictive for AIDS?. Lancet 2, 344.

    Article  PubMed  CAS  Google Scholar 

  • Campistol, J. M., Gutierrez-Dalmau, A., and Torregrosa, J. V. (2004). Conversion to sirolimus: a successful treatment for posttransplantation Kaposi’s sarcoma. Transplantation 77, 760–762.

    Article  PubMed  Google Scholar 

  • Carroll, P. A., Kenerson, H. L., Yeung, R. S., and Lagunoff, M. (2006). Latent Kaposi’s sarcoma-associated herpesvirus infection of endothelial cells activates hypoxia-induced factors. J Virol 80, 10802–10812.

    Article  PubMed  CAS  Google Scholar 

  • Centers for Disease Control. (1981). Kaposi’s sarcoma and Pneumocystis pneumonia among homosexual men – New York City and California. MMWR Morb Mortal Wkly Rep 30, 305–308.

    Google Scholar 

  • Chang, J., Renne, R., Dittmer, D., and Ganem, D. (2000). Inflammatory cytokines and the reactivation of Kaposi’s sarcoma-associated herpesvirus lytic replication. Virology 266, 17–25.

    Article  CAS  Google Scholar 

  • Chang, Y., Cesarman, E., Pessin, M. S., et al. (1994). Identification of herpesvirus-like DNA sequences in AIDS-associated Kaposi’s sarcoma. Science 266, 1865–1869.

    Article  PubMed  CAS  Google Scholar 

  • Coscoy, L., and Ganem, D. (2000). Kaposi’s sarcoma-associated herpesvirus encodes two proteins that block cell surface display of MHC class I chains by enhancing their endocytosis. Proc Natl Acad Sci USA 97, 8051–8056.

    Article  PubMed  CAS  Google Scholar 

  • D’Agostino, G., Arico, E., Santodonato, L., et al. (1999). Type I consensus IFN (IFN-con1) gene transfer into KSHV/HHV-8-infected BCBL-1 cells causes inhibition of viral lytic cycle activation via induction of apoptosis and abrogates tumorigenicity in SCID mice. J Interferon Cytokine Res 19, 1305–1316.

    Article  PubMed  Google Scholar 

  • Davey, R. T., Jr, Davey, V. J., Metcalf, J. A., et al. (1991). A phase I/II trial of zidovudine, interferon-alpha, and granulocyte-macrophage colony-stimulating factor in the treatment of human immunodeficiency virus type 1 infection. J Infect Dis 164, 43–52.

    Article  PubMed  Google Scholar 

  • Deichmann, M., Thome, M., Jackel, A., et al. (1998). Non-human immunodeficiency virus Kaposi’s sarcoma can be effectively treated with low-dose interferon-α despite the persistence of herpesvirus-8. Br J Dermatol 139, 1052–1054.

    Article  PubMed  CAS  Google Scholar 

  • De Leede, L. G., Humphries, J. E., Bechet, A. C., Van Hoogdalem, E. J., Verrijk, R., and Spencer, D. G. (2008). Novel controlled-release Lemna-derived IFN-alpha2b (Locteron): pharmacokinetics, pharmacodynamics, and tolerability in a phase I clinical trial. J Interferon Cytokine Res 28, 113–122.

    Article  PubMed  CAS  Google Scholar 

  • DeStefano, E., Friedman, R. M., Friedman-Kien, A. E., et al. (1982). Acid-labile human leukocyte interferon in homosexual men with Kaposi’s sarcoma and lymphadenopathy. J Infect Dis 146, 451–455.

    Article  PubMed  CAS  Google Scholar 

  • deWit, R., Reiss, P., Bakker, P. J., Lange, J. M., Danner, S. A., and Veenhof, K. H. (1989). Lack of activity of zidovudine in AIDS-associated Kaposi’s sarcoma. AIDS 3, 847–850.

    Article  CAS  Google Scholar 

  • deWit, R., Schattenkerk, J. K., Boucher, C. A., Bakker, P. J., Veenhof, K. H., and Danner, S. A. (1988). Clinical and virological effects of high-dose recombinant interferon-alpha in disseminated AIDS-related Kaposi’s sarcoma. Lancet 2, 1214–1217.

    Google Scholar 

  • deWit, R., Danner, S. A., Bakker, P. J., et al. (1991). Combined zidovudine and interferon-alpha treatment in patients with AIDS-associated Kaposi’s sarcoma. J Intern Med 229, 35–40.

    Article  PubMed  Google Scholar 

  • Evans, L. M., Itri, L. M., Campion, M., et al. (1991). Interferon-alpha 2a in the treatment of acquired immunodeficiency syndrome-related Kaposi’s sarcoma. J Immunother 10, 39–50.

    Article  PubMed  CAS  Google Scholar 

  • Eyster, M. E., Goedert, J. J., Poon, M.-C., and Preble, O. T. (1983). Acid-labile interferon. A possible preclinical marker for the acquired immunodeficiency syndrome in hemophilia. N Engl J Med 309, 583–586.

    Article  PubMed  CAS  Google Scholar 

  • Feldman, S., Stein, D., Amrute, S., et al. (2001). Decreased interferon-alpha production in HIV-infected patients correlates with numberical and functional deficiencies in circulating type 2 dendritic cell precursors. Clin Immunol 101, 201–210.

    Article  PubMed  CAS  Google Scholar 

  • Fischl, M. A., Gorowski, E., Koch, G., et al.. (1987). Interferon alfa-n1 Wellferon® in Kaposi’s sarcoma: single agent or combination with vinblastine. In: The Biology of the Interferon System 1986. pp. 355–362 (Boston: Martinus Nijhoff).

    Chapter  Google Scholar 

  • Fischl, M. A., Uttamchandani, R. B., Resnick, L., et al. (1991). A phase I study of recombinant human interferon-alpha 2a or human lymphoblastoid interferon-alpha n1 and concomitant zidovudine in patients with AIDS-related Kaposi’s sarcoma. J Acquir Immune Defic Syndr 4, 1–10.

    Article  PubMed  CAS  Google Scholar 

  • Fischl, M. A., Finkelstein, D. M., He, W., Powderly, W. G., Triozzi, P. L., and Steigbigel, R. T. (1996). A phase II study of recombinant human interferon-alpha 2a and zidovudine in patients with AIDS-related Kaposi’s sarcoma. AIDS Clinical Trials Group. J Acquir Immune Defic Syndr Hum Retrovirol 11, 379–384.

    Article  PubMed  CAS  Google Scholar 

  • Frissen, P. H., de Wolf, F., Reiss, P., et al. (1997). High-dose interferon-alpha2a exerts potent activity against human immunodeficiency virus type 1 not associated with antitumor activity in subjects with Kaposi’s sarcoma. J Infect Dis 176, 811–814.

    Article  PubMed  CAS  Google Scholar 

  • Fu, D. X., Tanhehco, Y. C., Chen, J., et al. (2007). Virus-associated tumor imaging by induction of viral gene expression. Clin Cancer Res 13, 1453–1458.

    Article  PubMed  CAS  Google Scholar 

  • Fu, D. X., Tanhehco, Y., Chen, J., et al. (2008). Bortezomib-induced enzyme-targeted radiation therapy in herpesvirus-associated tumors. Nat Med 14, 1118–1122.

    Article  PubMed  CAS  Google Scholar 

  • Fuchs, D., Hausen, A., Reibnegger, G., et al. (1989). Interferon-γ concentrations are increased in sera from individuals infected with human immunodeficiency virus type I. J Acquir Immune Defic Syndr 2, 158–162.

    PubMed  CAS  Google Scholar 

  • Ganju, R. K., Munshi, N., Nair, B. C., Liu, Z. Y., Gill, P., and Groopman, J. E. (1998). Human immunodeficiency virus tat modulates the Flk-1/KDR receptor, mitogen-activated protein kinases, and components of focal adhesion in Kaposi’s sarcoma cells. J Virol 72, 6131–6137.

    PubMed  CAS  Google Scholar 

  • Ganser, A., Brücher, W., Brodt, H. R., et al. (1986). Treatment of AIDS-related Kaposi’s sarcoma with recombinant gamma-interferon. Onkologie 9, 163–166.

    Article  PubMed  CAS  Google Scholar 

  • Gelmann, E. P., Preble, O. T., Steis, R., et al. (1985). Human lymphoblastoid interferon treatment of Kaposi’s sarcoma in the acquired immune deficiency syndrome. Clinical response and prognostic parameters. Am J Med 78, 737–741.

    Article  PubMed  CAS  Google Scholar 

  • Giraldo, G., Beth, E., and Haguenau, F. (1972). Herpes-type virus particles in tissue culture of Kaposi’s sarcoma from different geographic regions. J Natl Cancer Inst 49, 1509–1526.

    PubMed  CAS  Google Scholar 

  • Giraldo, G., Beth, E., Kourilsky, F. M., et al. (1975). Antibody patterns to herpesviruses in Kaposi’s sarcoma: serological association of european Kaposi’s sarcoma with cytomegalovirus. Int J Cancer 15, 839–848.

    Article  PubMed  CAS  Google Scholar 

  • Giraldo, G., Beth, E., Henle, W., et al. (1978). Antibody patterns to herpesviruses in Kaposi’s sarcoma. II. Serological association of American Kaposi’s sarcoma with cytomegalovirus. Int J Cancer 22, 126–131.

    Article  PubMed  CAS  Google Scholar 

  • Groopman, J. E., Gottlieb, M. S., Goodman, J., et al. (1984). Recombinant alpha-2 interferon therapy for Kaposi’s sarcoma associated with the acquired immunodeficiency syndrome. Ann Intern Med 100, 671–676.

    PubMed  CAS  Google Scholar 

  • Hartshorn, K. L., Vogt, M. W., Chou, T. C., et al. (1987). Synergistic inhibition of human immunodeficiency virus in vitro by azidothymidine and recombinant alpha A interferon. Antimicrob Agents Chemother 31, 168–172.

    Article  PubMed  CAS  Google Scholar 

  • Ho, D. D., Hartshorn, K. L., Rota, T. R., et al. (1985). Recombinant human interferon alfa-A suppresses HTLV-III replication in vitro. Lancet 1, 602–604.

    Article  PubMed  CAS  Google Scholar 

  • Huber, C. H., Batchelor, B. R., Fuchs, D., et al. (1984). Immune response-associated production of neopterin. Release from macrophages primarily under control of interferon-gamma. J Exp Med 160, 310–316.

    Article  PubMed  CAS  Google Scholar 

  • Ishido, S., Wang, C., Lee, B. S., Cohen, G. B., and Jung, J. U. (2000). Downregulation of major histocompatibility complex class I molecules by Kaposi’s sarcoma-associated herpesvirus K3 and K5 proteins. J Virol 74, 5300–5309.

    Article  PubMed  CAS  Google Scholar 

  • Johnson, V. A., Merrill, D. P., Videler, J. A., et al. (1991). Two-drug combinations of zidovudine, didanosine, and recombinant interferon-alpha A inhibit replication of zidovudine-resistant human immunodeficiency virus type 1 synergistically in vitro. J Infect Dis 164, 646–655.

    Article  PubMed  CAS  Google Scholar 

  • Jacobson, M. A., Bacchetti, P., Kolokathis, A., et al. (1991). Surrogate markers for survival in patients with AIDS and AIDS related complex treated with zidovudine. BMJ 302, 73–78.

    Article  PubMed  CAS  Google Scholar 

  • Kaur, S., Lal, L., Sassano, A., et al. (2007). Regulatory effects of mammalian target of rapamycin-activated pathways in type I and II interferon signaling. J Biol Chem 282, 1757–1768.

    Article  PubMed  CAS  Google Scholar 

  • Kern, P., Meigel, W., Rácz, P., Gottesleben, A., Dettke, T., and Dietrich, M. (1987). Interferon alpha in the treatment of AIDS-associated Kaposi’s sarcoma. Onkologie 10, 50–52.

    Article  PubMed  CAS  Google Scholar 

  • Klass, C. M., and Offermann, M. K. (2005). Targeting human herpesvirus-8 for treatment of Kaposi’s sarcoma and primary effusion lymphoma. Curr Opinion Oncol 17, 447–455.

    Article  CAS  Google Scholar 

  • Klass, C. M., Krug, L. T., Pozharskaya, V. P., and Offermann, M. K. (2005). The targeting of primary effusion lymphoma cells for apoptosis by inducing lytic replication of human herpesvirus 8 while blocking virus production. Blood 105, 4028–4034.

    Article  PubMed  CAS  Google Scholar 

  • Koon, H. B., Bubley, G. J., Pantanowitz, L., et al. (2005). Imatinib-induced regression of AIDS-related Kaposi’s sarcoma. J Clin Oncol 23, 982–989.

    Article  PubMed  CAS  Google Scholar 

  • Kovacs, J. A., Deyton, L., Davey, R., et al. (1989). Combined zidovudine and interferon-alpha therapy in patients with Kaposi sarcoma and the acquired immunodeficiency syndrome (AIDS). Ann Intern Med 111, 280–287.

    PubMed  CAS  Google Scholar 

  • Krigel, R. L., Odajnyk, C. M., Laubenstein, L. J., et al. (1985). Therapeutic trial of interferon-gamma in patients with epidemic Kaposi’s sarcoma. J Biol Response Mod 4, 358–364.

    PubMed  CAS  Google Scholar 

  • Krigel, R. L., Slywotzky, C. M., Lonberg, M., et al. (1988). Treatment of epidemic Kaposi’s sarcoma with a combination of interferon-alpha 2b and etoposide. J Biol Response Mod 7, 359–364.

    PubMed  CAS  Google Scholar 

  • Krown, S. E. (2004). Highly active antiretroviral therapy in AIDS-associated Kaposi’s sarcoma: implications for the design of therapeutic trials in patients with advanced, symptomatic Kaposi’s sarcoma. J Clin Oncol 22, 399–402.

    Article  PubMed  Google Scholar 

  • Krown, S. E., Real, F. X., Cunningham-Rundles, S., et al. (1983). Preliminary observations on the effect of recombinant leukocyte A interferon in homosexual men with Kaposi’s sarcoma. New Engl J Med 308, 1071–1076.

    Article  PubMed  CAS  Google Scholar 

  • Krown, S. E., Real, F. X., Vadhan-Raj, S., Cunningham-Rundles, S., Krim, M., Wong, G., et al. (1986). Kaposi’s sarcoma and the acquired immunodeficiency syndrome: treatment with recombinant interferon alpha and analysis of prognostic factors. Cancer 57(Suppl), 1662–1665.

    Article  PubMed  CAS  Google Scholar 

  • Krown, S. E., Gold, J. W. M., Niedzwiecki, D., et al. (1990). Interferon alpha with zidovudine: safety, tolerance and clinical and virological effects in patients with Kaposi sarcoma associated with the acquired immunodeficiency syndrome (AIDS). Ann Intern Med 112, 812–821.

    PubMed  CAS  Google Scholar 

  • Krown, S. E., Niedzwiecki, D., Bhalla, R., Flomenberg, N., Bundow, D., and Chapman, D. (1991). Relationship and prognostic value of endogenous interferon alpha, beta2-microglobulin and neopterin serum levels in patients with Kaposi sarcoma and acquired immunodeficiency syndrome (AIDS). J Acquir Immune Defic Syndr 4, 871–880.

    Article  PubMed  CAS  Google Scholar 

  • Krown, S. E., Paredes, J., Bundow, D., Polsky, B., Gold, J. W. M., and Flomenberg, N. (1992). Interferon-α, zidovudine and granulocyte-macrophage colony-stimulating factor: a phase I trial in patients with Kaposi sarcoma associated with the acquired immunodeficiency syndrome (AIDS). J Clin Oncol 10, 1344–1351.

    PubMed  CAS  Google Scholar 

  • Krown, S. E., Li, P., Von Roenn, J. H., Paredes, J., Huang, J., and Testa, M. A. (2002). Randomized, open-label, phase II AIDS Clinical Trials Group study of two doses of interferon alfa-2b combined with didanosine in patients with AIDS-associated Kaposi’s sarcoma: efficacy of daily low-dose interferon. J Interferon Cytokine Res 22, 295–303.

    Article  PubMed  CAS  Google Scholar 

  • Krown, S. E., Lee, J. Y., Lin, L., Fischl, M. A., Ambinder, R., and VonRoenn, J. H. (2006). A phase I trial of protease inhibitor-based antiretroviral therapy with recombinant interferon alfa-2b in patients with HIV-related Kaposi’s sarcoma. J Acquired Immun Defic Syndr 41, 149–153.

    Article  CAS  Google Scholar 

  • Krown, S. E., Lee, J. Y., and Dittmer, D. D. (2008). More on HIV-associated Kaposi’s sarcoma. N Engl J Med 358, 535–536.

    Article  PubMed  CAS  Google Scholar 

  • Krug, L. T., Pozharskaya, V. P., Yu, Y., Inoue, N., and Offermann, M. K. (2004). Inhibition of infection and replication of human herpesvirus 8 in microvascular endothelial cells by α interferon and phosphonoformic acid. J Virol 78, 8359–8371.

    Article  PubMed  CAS  Google Scholar 

  • Lagos, D., Trotter, M. W., Vart, R. J., et al. (2007). Kaposi sarcoma herpesvirus-encoded vFLIP and vIRF1 regulate antigen presentation in lymphatic endothelial cells. Blood 109, 1550–1558.

    Article  PubMed  CAS  Google Scholar 

  • Lane, H. C., Kovacs, J. A., Feinberg, J., et al. (1988). Anti-retroviral effects of interferon-alpha in AIDS-associated Kaposi’s sarcoma. Lancet 2, 1218–1222.

    Article  PubMed  CAS  Google Scholar 

  • Lane, H. C., Davey, R. T., Jr, Sherwin, S. A., et al. (1989a). A phase I trial of recombinant human interferon-gamma in patients with Kaposi’s sarcoma and the acquired immunodeficiency syndrome (AIDS). J Clin Immunol 9, 351–361.

    Article  PubMed  CAS  Google Scholar 

  • Lane, H. C., Falloon, J., Walker, R. E., et al. (1989b). Zidovudine in patients with human immunodeficiency virus (HIV) infection and Kaposi sarcoma. A phase II randomized, placebo-controlled trial. Ann Intern Med 111, 41–50.

    PubMed  CAS  Google Scholar 

  • Lang, A., Niederwieser, D., and Huber, C. (1984). Treatment with recombinant interferon alpha-2 induces increase of in vivo neopterin excretion. In: Pfleiderer, W., Wachter, H., and Curtius, H. C., eds. Biochemical and Clinical Aspects of Pteridines, Vol 3. pp. 251–254 (Berlin: Walter de Gruyter).

    Google Scholar 

  • Lau, A. S., Read, S. E., and Williams, B. R. (1988). Downregulation of interferon alpha but not gamma receptor expression in vivo in the acquired immunodeficiency syndrome. J Clin Invest 82, 1415–1421.

    Article  PubMed  CAS  Google Scholar 

  • Lau, A. S., and Livesy, J. F. (1989). Endotoxin induction of tumor necrosis factor is enhanced by acid-labile interferon-alpha in acquired immunodeficiency syndrome. J Clin Invest 84, 738–743.

    Article  PubMed  CAS  Google Scholar 

  • Lebbe, C., de Cremoux, P., Millot, G., et al. (1997). Characterization of in vitro culture of HIV-negative Kaposi’s sarcoma-derived cells. In vitro responses to alfa interferon. Arch Dematol Res 289, 421–428.

    CAS  Google Scholar 

  • Little, R. F., Pluda, J. M., Wyvill, K. M., et al. (2006). Activity of subcutaneous interleukin-12 in AIDS-related Kaposi sarcoma. Blood 107, 4650–4657.

    Article  PubMed  CAS  Google Scholar 

  • Lopez, C., Fitzgerald, P. A., and Siegal, F. (1983). Severe acquired immune deficiency syndrome in male homosexuals. Diminished capacity to make interferon-α in vitro associated with severe opportunistic infections. J Infect Dis 148, 962–977.

    Article  PubMed  CAS  Google Scholar 

  • Marchisone, C., Benelli, R., Albini, A., Santi, L., and Noonan, D. M. (1999). Inhibition of angiogenesis by type I interferons in models of Kaposi’s sarcoma. Int J Biol Markers 14, 257–262.

    PubMed  CAS  Google Scholar 

  • Maurer, T., Ponte, M., and Leslie, K. (2007). HIV-associated Kaposi’s sarcoma with a high CD4 count and a low viral load. N Engl J Med 357, 1352–1353.

    Article  PubMed  CAS  Google Scholar 

  • Mauss, S., and Jablonowski, H. (1995). Efficacy, safety, and tolerance of low-dose, long-term interferon-alpha 2b and zidovudine in early-stage AIDS-associated Kaposi’s sarcoma. J Acquir Immune Defic Syndr Hum Retrovirol 10, 157–162.

    Article  PubMed  CAS  Google Scholar 

  • Mercader, M., Taddeo, B., Panella, J. R., Chandran, B., Nickoloff, B. J., and Foreman, K. E. (2000). Induction of HHV-8 lytic cycle replication by inflammatory cytokines produced by HIV-1-infected T cells. Am J Pathol 156, 1961–1971.

    Article  PubMed  CAS  Google Scholar 

  • Mildvan, D., Machado, S. G., Wilets, I., and Grossberg, S. E. (1992). Endogenous interferon and triglyceride concentrations to assess response to zidovudine in AIDS and advanced AIDS-related complex. Lancet 339, 453–456.

    Article  PubMed  CAS  Google Scholar 

  • Mildvan, D., Bassiakos, Y., Zucker, M. L., et al. (1996). Synergy, activity and tolerability of zidovudine and interferon-alpha in patients with symptomatic HIV-1 infection: AIDS Clinical Trial Group 068. Antivir Ther 1, 77–88.

    PubMed  CAS  Google Scholar 

  • Mildvan, D., Spritzler, J., Grossberg, S. E., et al. (2005). Serum neopterin, an immune activation marker, independently predicts disease progression in advanced HIV-1 infection. Clin Infect Dis 40, 853–858.

    Article  PubMed  CAS  Google Scholar 

  • Miles, S. A., Martinez, O., Sherwin, S., et al. (1986). Phase I trial of recombinant interferon gamma in AIDS-related Kaposi’s sarcoma. Proceedings of the 2nd International Conference on AIDS. Paris, France, p. 36.

    Google Scholar 

  • Miles, S. A., Wang, H. J., Cortes, E., Carden, J., Marcus, S., and Mitsuyasu, R. T. (1990). Beta-interferon therapy in patients with poor-prognosis Kaposi sarcoma related to the acquired immunodeficiency syndrome (AIDS). A phase II trial with preliminary evidence of antiviral activity and low incidence of opportunistic infections. Ann Intern Med 112, 582–589.

    PubMed  CAS  Google Scholar 

  • Miles, S., Levine, A., Feldstein, M., et al. (1998). Open-label phase I study of combination therapy with zidovudine and interferon-beta in patients with AIDS-related Kaposi’s sarcoma: AIDS Clinical Trials Group Protocol 057. Cytokines Cell Mol Ther 4, 17–23.

    PubMed  CAS  Google Scholar 

  • Milligan, S., Robinson, M., O’Donnell, E., and Blackbourn, D. J. (2004). Inflammatory cytokines inhibit kaposi’s sarcoma-associated herpesvirus lytic gene transcription in in vitro-infected endothelial cells. J Virol 78, 2591–2596.

    Article  PubMed  CAS  Google Scholar 

  • Mitsuyasu, R. T., Taylor, J. M., Glaspy, J., and Fahey, J. L. (1986). Heterogeneity of epidemic Kaposi’s sarcoma. Implications for therapy. Cancer 57(8 Suppl), 1657–1661.

    Article  PubMed  CAS  Google Scholar 

  • Monini, P., Carlini, F., Sturzl, M., et al. (1999). Alpha interferon inhibits human herpesvirus 8 (HHV-8) reactivation in primary effusion lymphoma cells and reduces HHV-8 load in cultured peripheral blood mononuclear cells. J Virol 73, 4029–4041.

    PubMed  CAS  Google Scholar 

  • Monini, P., Sirianni, M. C., Franco, M., et al. (2001). Clearance of human herpesvirus 8 from blood and regression of leucopenia-associated aggressive classic Kaposi’s sarcoma during interferon-α therapy: a case report. Clin Infect Dis 33, 1782–1785.

    Article  PubMed  CAS  Google Scholar 

  • Montaner, S. (2007). Akt/TSC/mTOR activation by the KSHV G protein-coupled receptor: emerging insights into the molecular oncogenesis and treatment of Kaposi’s sarcoma. Cell Cycle 6, 438–443.

    Article  PubMed  CAS  Google Scholar 

  • Murray, H. W., Rubin, B. J., Masur, H., and Roberts, R. B. (1984). Impaired production of lymphokines and immune (gamma) interferon in the acquired immunodeficiency syndrome. N Engl J Med 310, 883–889.

    Article  PubMed  CAS  Google Scholar 

  • Murray, H. W., Gellene, R. A., Libby, D. M., Rothermel, C. D., and Rubin, B. Y. (1985). Activation of tissue macrophages from AIDS patients: in vitro response of AIDS alveolar macrophages to lymphokines and interferon-gamma. J Immunol 135, 2374–2377.

    PubMed  CAS  Google Scholar 

  • Niedermeier, A., Talanin, N., Chung, E. J., et al. (2006). Histone deacetylase inhibitors induce apoptosis with minimal viral reactivation in cells infected with Kaposi’s sarcoma-associated herpesvirus. J Invest Dermatol 126, 2516–2524.

    Article  PubMed  CAS  Google Scholar 

  • Offermann, M. K. (2007). Kaposi sarcoma herpesvirus-encoded interferon regulatory factors. Curr Top Microbiol Immunol 312, 185–209.

    Article  PubMed  CAS  Google Scholar 

  • Parmar, S., Smith, J., Sassano, A., et al. (2005). Differential regulation of the p70 S6 kinase pathway by interferon alpha (IFNalpha) and imatinib mesylate (STI571) in chronic myelogenous leukemia cells. Blood 106, 2436–2443.

    Article  PubMed  CAS  Google Scholar 

  • Penn, I. (1979). Kaposi’s sarcoma in organ transplant recipients: report of 20 cases. Transplantation 27, 8–11.

    Article  PubMed  CAS  Google Scholar 

  • Pitha, P. M. (1994). Multiple effects of interferon on the replication of human immunodeficiency virus type 1. Antiviral Res 24, 205–219.

    Article  PubMed  CAS  Google Scholar 

  • Pitha, P. M., Au, W. C., Lowther, W., et al. (1998). Role of the interferon regulatory factors (IRFs) in virus-mediated signaling and regulation of cell growth. Biochimie 80, 651–658.

    Article  PubMed  CAS  Google Scholar 

  • Podzamczer, D., Bolao, F., Clotet, B., et al. (1993). Low-dose interferon alpha combined with zidovudine in patients with AIDS-associated Kaposi’s sarcoma. J Intern Med 233, 247–253.

    Article  PubMed  CAS  Google Scholar 

  • Pozharskaya, V. P., Weakland, L. L., and Offermann, M. K. (2004a). Inhibition of infectious human herpesvirus 8 production by gamma interferon and alpha interferon in BCBL-1 cells. J Gen Virol 85, 2779–2787.

    Article  PubMed  CAS  Google Scholar 

  • Pozharskaya, V. P., Weakland, L. L., Zimring, J. C., et al. (2004b). Short duration of elevated vIRF-1 expression during lytic replication of human herpesvirus 8 limits its ability to block antiviral responses induced by alpha interferon in BCBL-1 cells. J Virol 78, 6621–6635.

    Article  PubMed  CAS  Google Scholar 

  • Preble, O. T., Rook, A. H., Steis, R., et al. (1985). Interferon-induced 2ʹ-5ʹ oligoadenylate synthetase during interferon-alpha therapy in homosexual men with Kaposi’s sarcoma: marked deficiency in biochemical response to interferon in patients with acquired immunodeficiency syndrome. J Infect Dis 152, 457–465.

    Article  PubMed  CAS  Google Scholar 

  • Real, F. X., Oettgen, H. F., and Krown, S. E. (1986). Kaposi’s sarcoma and the acquired immunodeficiency syndrome: treatment with high and low doses of recombinant leukocyte A interferon. J Clin Oncol 4, 544–551.

    PubMed  CAS  Google Scholar 

  • Reiter, Z., Ozes, O. N., Blatt, L. M., Sturzl, M., and Taylor, M. W. (1992). A possible role for interferon-alpha and activated natural killer cells in remission of AIDS-related Kaposi’s sarcoma: in vitro studies. J Acquir Immune Defic Syndr 5, 469–476.

    Article  PubMed  CAS  Google Scholar 

  • Rezaee, S. A. R., Cunningham, C., Davison, A. J., and Blackbourn, D. J. (2006). Kaposi’s sarcoma-associated herpesvirus immune modulation: an overview. J Gen Virol 87, 1781–1804.

    Article  PubMed  CAS  Google Scholar 

  • Rios, A., Mansell, P. W., Newell, G. R., Reuben, J. M., Hersh, E. M., and Gutterman, J. U. (1985). Treatment of acquired immunodeficiency syndrome – related Kaposi’s sarcoma with lymphoblastoid interferon. J Clin Oncol 3, 506–512.

    PubMed  CAS  Google Scholar 

  • Rozenbaum, W., Gharakhanian, S., Navarette, M. S., De Sahb, R., Cardon, B., and Rouzioux, C. (1990). Long-term follow-up of 120 patients with AIDS-related Kaposi’s sarcoma treated with interferon alpha-2a. J Invest Dermatol 95(6 Suppl), 161S–165S.

    Article  PubMed  CAS  Google Scholar 

  • Scadden, D. T., Bering, H. A., Levine, J. D., et al. (1991). Granulocyte-macrophage colony-stimulating factor mitigates the neutropenia of combined interferon alfa and zidovudine treatment of acquired immune deficiency syndrome-associated Kaposi’s sarcoma. J Clin Oncol 9, 802–808.

    PubMed  CAS  Google Scholar 

  • Shaw, R. N., Arbiser, J. L., and Offermann, M. K. (2000). Valproic acid induces human herpesvirus 8 lytic gene expression in BCBL-1 cells. AIDS 14, 899–902.

    Article  PubMed  CAS  Google Scholar 

  • Shepherd, F. A., Evans, W. K., Garvey, B., et al. (1988). Combination chemotherapy and alpha-interferon in the treatment of Kaposi’s sarcoma associated with acquired immune deficiency syndrome. CMAJ 139, 635–639.

    PubMed  CAS  Google Scholar 

  • Shepherd, F. A., Beaulieu, R., Gelmon, K., et al. (1998). Prospective randomized trial of two dose levels of interferon alfa with zidovudine for the treatment of Kaposi’s sarcoma associated with human immunodeficiency virus infection: a Canadian HIV Clinical Trials Network study. J Clin Oncol 16, 1736–1742.

    PubMed  CAS  Google Scholar 

  • Shin, Y. C., Joo, C.-H., Gack, M. U., Lee, H.-R., and Jung, J. U. (2008). Kaposi’s sarcoma-associated herpesvirus viral IFN regulatory factor 3 stabilizes hypoxia-inducible factor-1α to induce vascular endothelial growth factor expression. Cancer Res 68, 1751–1759.

    Article  PubMed  CAS  Google Scholar 

  • Siegel, F. P., Lopez, C., Fitzgerald, P. A., et al. (1986). Opportunistic infections in acquired immune deficiency syndrome result from synergistic defects of both the natural and adaptive components of cellular immunity. J Clin Invest 78, 115–123.

    Article  Google Scholar 

  • Siegel, F. P., Fitzgerald-Bocarsly, P., Holland, B. K., and Shodell, M. (2001). Interferon-alpha generation and immune reconstitution during antiretroviral therapy for human immunodeficiency virus infection. AIDS 15, 1603–1612.

    Article  Google Scholar 

  • Sirianni, M. C., Vincenzi, L., Topino, S., et al. (2002). NK cell activity controls human herpesvirus 8 latent infection and is restored upon highly active antiretroviral therapy in AIDS patients with regressing Kaposi’s sarcoma. Eur J Immunol 32, 2711–2720.

    Article  PubMed  CAS  Google Scholar 

  • Soumelis, V., Scott, I., Gheyas, F., et al. (2001). Depletion of circulating natural type 1 interferon-producing cells in HIV-infected AIDS patients. Blood 98, 906–912.

    Article  PubMed  CAS  Google Scholar 

  • Stadler, R., Bratzke, B., Schaart, F., and Orfanos, C. E. (1990). Long-term combined rIFN-alpha-2a and zidovudine therapy for HIV-associated Kaposi’s sarcoma: clinical consequences and side effects. J Invest Dermatol 95(6 Suppl), 170S–175S.

    Article  PubMed  CAS  Google Scholar 

  • Stallone, G., Schena, A., Infante, B., et al. (2005). Sirolimus for Kaposi’s sarcoma in renal-transplant recipients. N Engl J Med 352, 1317–1323.

    Article  PubMed  CAS  Google Scholar 

  • Staskus, K. A., Zhong, W., Gebhard, K., et al. (1997). Kaposi’s sarcoma-associated herpesvirus gene expression in endothelial (spindle) tumor cells. J Virol 71, 715–719.

    PubMed  CAS  Google Scholar 

  • Subramanian, G. M., Fiscella, M., Lamousé-Smith, A., Zeuzem, S., and McHutchison, J. G. (2007). Albinterferon alpha-2b: a genetic fusion protein for the treatment of chronic hepatitis C. Nat Biotechnol 25, 1411–1419.

    Article  PubMed  CAS  Google Scholar 

  • Tomlinson, C. C., and Damania, B. (2004). The K1 protein of Kaposi’s sarcoma-associated herpesvirus activates the Akt signaling pathway. J Virol 78, 1918–1927.

    Article  PubMed  CAS  Google Scholar 

  • Vadhan-Raj, S., Wong, G., Gnecco, C., et al. (1986). Immunological variables as predictors of prognosis in patients with Kaposi’s sarcoma and the acquired immunodeficiency syndrome. Cancer Res 46, 417–425.

    PubMed  CAS  Google Scholar 

  • Vogt, M. W., Durno, A. G., Chou, T. C., et al. (1988). Synergistic interaction of 2ʹ,3ʹ-dideoxycytidine and recombinant interferon-alpha-A on replication of human immunodeficiency virus type 1. J Infect Dis 158, 378–385.

    Article  PubMed  CAS  Google Scholar 

  • Volberding, P. A., Mitsuyasu, R. T., Golando, J. P., and Spiegel, R. J. (1987). Treatment of Kaposi’s sarcoma with interferon alfa-2b (Intron A). Cancer 59(3 Suppl), 620–625.

    Article  PubMed  CAS  Google Scholar 

  • vonMarschall, Z., Scholz, A., Cramer, T., et al. (2003). Effects of interferon alpha on vascular endothelial growth factor gene transcription and tumor angiogenesis. J Natl Cancer Inst 95, 437–448.

    Article  CAS  Google Scholar 

  • Wang, L., and Damania, B. (2008). Kaposi’s sarcoma-associated herpesvirus confers a survival advantage to endothelial cells. Cancer Res 68, 4640–4648.

    Article  PubMed  CAS  Google Scholar 

  • Wang, H.-W., Trotter, M. W., Lagos, D., et al. (2004). Kaposi sarcoma herpesvirus-induced cellular reprogramming contributes to the lymphatic endothelial gene expression in Kaposi sarcoma. Nat Genet 36, 687–693.

    Article  PubMed  CAS  Google Scholar 

  • Wu, W.-Z., Sun, H.-C., Shen, Y.-F., et al. (2005). Interferon alpha 2a downregulates VEGF expression through PI3 kinase and MAP kinase signaling pathways. J Cancer Res Clin Oncol 131, 169–178.

    Article  PubMed  CAS  Google Scholar 

  • Yu, Y., Wang, S. E., and Hayward, G. S. (2005). The KSHV immediate-early transcription factor RTA encodes ubiquitin E3 ligase activity that targets IRF7 for proteosome-mediated degradation. Immunity 22, 59–70.

    Article  PubMed  CAS  Google Scholar 

  • Zhu, F. X., King, S. M., Smith, E. J., Levy, D., and Yuan, Y. (2002). A Kaposi’s sarcoma-associated herpesviral protein inhibits virus-mediated induction of type I interferon by blocking IRF-7 phosphorylation and nuclear accumulation. Proc Natl Acad Sci USA 99, 5573–5578.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Melanoma and Sarcoma Service, Division of Solid Tumor Oncology, Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY, USA

    Susan E. Krown

Authors
  1. Susan E. Krown
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Susan E. Krown .

Editor information

Editors and Affiliations

  1. Lineberger Comprehensive, Cancer Center, University of North Carolina, Chapel Hill, North Carolina, USA

    Dirk P. Dittmer

  2. Cancer Center, Memorial Sloan-Kettering, York Ave. 1275, New York, 10065, New York, USA

    Susan E. Krown

Rights and permissions

Reprints and permissions

Copyright information

© 2010 Springer Science+Business Media, LLC

About this chapter

Cite this chapter

Krown, S.E. (2010). Interferon in Kaposi’s Sarcoma Biology and Therapy. In: Dittmer, D., Krown, S. (eds) Molecular Basis for Therapy of AIDS-Defining Cancers. Springer, New York, NY. https://doi.org/10.1007/978-1-4419-1513-9_11

Download citation

Publish with us

Policies and ethics

Search

Navigation