Interferon-inducible protein 10 as a possible factor in the pathogenesis of cutaneous T-cell lymphomas

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

Research output: Contribution to journalArticle

22 Scopus citations

Abstract

Human IFN-γ-inducible protein 10 (IP-10), a C-X-C chemokine secreted by IFN-γ-stimulated keratinocytes, is chemotactic for normal CD4-positive lymphocytes and inhibits the proliferation of early subsets of normal and of leukemic hemopoietic progenitors. Cutaneous T-cell lymphoma (CTCL) is an indolent lymphoproliferative disorder of CD4-positive lymphocytes that remain confined to the skin for many years before visceral dissemination. Because IFN-γ mRNA was detected in the epidermis of CTCL lesions, we decided to investigate the role of IP-10 in the epidermotropism of CTCL by determining its expression in normal skin and in CTCL lesions. Using purified recombinant IP-10 (rIP-10) or a recombinant fusion protein between IP-l0 and the Φ10 protein of phage T7, we generated rabbit antisera that recognized and neutralized rIP-10. Immunoperoxidase staining of normal epidermis demonstrated that IP-10 was expressed by basal keratinocytes but not by the more differentiated cells. In the often hyperplastic epidermis overlying CTCL lesions, IP-10 immunostaining was enhanced compared to normal skin and extended to the suprabasal keratinocytes in 28 of 29 patients for a frequency of 97% and a 95% confidence interval of 82-100%. However, IP-10 was detectable in the dermal or epidermal lymphoid infiltrates in only 3 of 29 patients (10%; 95% confidence interval, 2-29%). 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 overexpressed before treatment but was normally expressed at remission. The in vitro proliferation of primary normal human keratinocytes was inhibited in a dose-dependent manner by rIP-10. These results suggest that IP-10 plays a role in the epidermotropism of CTCL. Additional work is needed to determine whether IP-10 stimulates or inhibits CTCL proliferation. A better understanding of the growth controls operating in CTCL may be useful in the development of curative strategies for this disorder.

Original languageEnglish (US)
Pages (from-to)169-177
Number of pages9
JournalClinical Cancer Research
Volume3
Issue number2
StatePublished - Mar 18 1997

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Sarris, A. H., Daliani, D., Ulmer, R., Crow, M., Broxmeyer, H. E., Reiss, M., Karasavvas, N., Zelenetz, A. D., Pugh, W., Cabanillas, F., Deisseroth, A. B., & Duvic, M. (1997). Interferon-inducible protein 10 as a possible factor in the pathogenesis of cutaneous T-cell lymphomas. Clinical Cancer Research, 3(2), 169-177.