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


Authors: 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.
Article Title: Interferon-inducible protein 10 as a possible factor in the pathogenesis of cutaneous T-cell lymphomas
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.
Keywords: immunohistochemistry; adult; clinical article; controlled study; human tissue; aged; aged, 80 and over; middle aged; unclassified drug; cell division; skin neoplasms; keratinocyte; skin tumor; t cell lymphoma; cytokines; gamma interferon; interferon-gamma; gamma interferon inducible protein 10; keratinocytes; interferon type ii; lymphoma, t-cell, cutaneous; chemokine cxcl10; chemokines, cxc; humans; human; male; female; priority journal; article
Journal Title: Clinical Cancer Research
Volume: 3
Issue: 2
ISSN: 1078-0432
Publisher: American Association for Cancer Research  
Date Published: 1997-02-01
Start Page: 169
End Page: 177
Language: English
PUBMED: 9815669
PROVIDER: scopus
DOI/URL:
Notes: Article -- Export Date: 17 March 2017 -- Source: Scopus
Citation Impact
MSK Authors
  1. Andrew D Zelenetz
    768 Zelenetz