Interferon-inducible protein-10 and the pathogenesis of cutaneous T-cell lymphomas

Andreas H. Sarris, Danai Daliani, Rose Ulmer, Mary Crow, Hal E. Broxmeyer, William Pugh, Michael Reiss, Fernando Cabanillas, Albert B. Deisseroth, Madeleine Duvic

Research output: Contribution to journalArticle

11 Scopus citations

Abstract

Human interferon-g inducible protein-10 (IP-10), a small basic protein secreted by interferon (INF)-g stimulated keratinocytes, is chemotactic for normal CD4-positive lymphocytes and inhibits early normal and leukemic hemopoietic progenitor proliferation. Cutaneous T-cell lymphoma (CTCL) is an indolent CD4-positive lymphoma characterized by multiple skin relapses before visceral dissemination. We investigated the role of IP-10 in the biology of CTCL by using immunocytochemistry to define IP-10 expression in normal and CTCL skin biopsies. Using purified recombinant (r) IP-10, we generated a rabbit antiserum that recognized and neutralized rIP-10 but did not cross-react with any keratinocyte proteins or any other chemokine. Immunoperoxidase staining of normal epidermis demonstrated that IP-10 was expressed by basal but not by differentiated keratinocytes. The epidermis overlying CTCL lesions was often hyperplastic, IP-10 immunostaining was enhanced compared to normal skin, and extended to the suprabasal keratinocytes in 25 of 26 patients for a frequency of 96%; and 95% confidence interval (CI) of 80% to 100%. However, IP-10 was detectable in the dermal or epidermal lymphoid infiltrates in only three of these 26 patients (12%; 95% CI, 2% to 39%). Skin clinically free of CTCL demonstrated normal IP-10 immunostaining. In one patient who had matching biopsies performed before and after treatment, IP-10 was initially overexpressed before treatment but was normally expressed when he achieved remission. These results suggest that IP-10 may play a role in the epidermotropism of CTCL. More work is required to determine whether IP-10 stimulates or inhibits CTCL proliferation. A better understanding of the growth controls operating in CTCL may be used to develop curative therapies for this disorder.

Original languageEnglish (US)
Pages (from-to)103-110
Number of pages8
JournalLeukemia and Lymphoma
Volume24
Issue number1-2
DOIs
StatePublished - Jan 1 1996
Externally publishedYes

Keywords

  • Cutaneous T-cell lymphomas
  • Interferon
  • Interferon-inducible protein
  • Pathogenesis
  • Protein-10

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research

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  • Cite this

    Sarris, A. H., Daliani, D., Ulmer, R., Crow, M., Broxmeyer, H. E., Pugh, W., Reiss, M., Cabanillas, F., Deisseroth, A. B., & Duvic, M. (1996). Interferon-inducible protein-10 and the pathogenesis of cutaneous T-cell lymphomas. Leukemia and Lymphoma, 24(1-2), 103-110. https://doi.org/10.3109/10428199609045718