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Prognostic significance of autoimmunity during treatment of melanoma with interferon

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Abstract

Since the pivotal cooperative group trials in the 1980’s-90’s,, high-dose interferon (HDI) has been the standard of adjuvant therapy. Despite multiple other trials evaluating potential new therapies in melanoma, HDI remains the only FDA-approved therapy for stage IIB and III melanoma. Initial reports from the more recent phase III international trials of modifications of the original HDI regimen linked the appearance of autoimmunity with improved outcomes of disease. Trials of high-dose interleukin-2, many years earlier, reported anecdotal observations that were consistent with the hypothesis that autoimmunity and clinical benefit of immunotherapies of melanoma are linked with one another. The only prospectively conducted study examining the appearance of clinical and laboratory evidence of autoimmunity during HDI therapy was published by Gogas and colleagues, demonstrating statistically significant impact on relapse-free survival and overall survival. Retrospectively conducted studies of different intermediate dosage regimens of interferon (IFN) have not fully confirmed the linkage of serological evidence of autoimmunity and improved survival outcomes. With the emergence of new immunotherapies in treatment of melanoma, this review highlights the importance of autoimmunity for future applications in melanoma and reviews significant differences of past studies evaluating the appearance of autoimmunity during IFN therapy in high-risk melanoma.

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Acknowledgments

This work was supported by Award Number P50CA121973 from the National Cancer Institute. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Cancer Institute or the National Institutes of Health.

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Authors and Affiliations

  1. Melanoma Program, University of Pittsburgh Cancer Institute, Pittsburgh, PA, USA

    Michal T. Krauze, Ahmad Tarhini & John M. Kirkwood

  2. Medical Oncology Division, 2nd Department of Medicine, University of Athens, Athens, Greece

    Helen Gogas

  3. Hillman Cancer Center, University of Pittsburgh Cancer Institute, Research Suite L1.32c, 5117 Centre Avenue, Pittsburgh, PA, 15213-2584, USA

    John M. Kirkwood

  4. Department of Medicine, University of Pittsburgh, Pittsburgh, PA, USA

    Michal T. Krauze, Ahmad Tarhini & John M. Kirkwood

Authors
  1. Michal T. Krauze
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  2. Ahmad Tarhini
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  3. Helen Gogas
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  4. John M. Kirkwood
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Correspondence to John M. Kirkwood.

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This article is published as part of the Special Issue on Prognostic Impact of Anti-Cancer Immune Responses.

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Krauze, M.T., Tarhini, A., Gogas, H. et al. Prognostic significance of autoimmunity during treatment of melanoma with interferon. Semin Immunopathol 33, 385–391 (2011). https://doi.org/10.1007/s00281-011-0247-y

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