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

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22 Scopus citations


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
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.