This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Ni, X. Articles by Duvic, M. Search for Related Content PubMed PubMed Citation Articles by Ni, X. Articles by Duvic, M.

Fas Ligand Expression by Neoplastic T Lymphocytes Mediates Elimination of CD8+ Cytotoxic T Lymphocytes in Mycosis Fungoides

A Potential Mechanism of Tumor Immune Escape?¹

Department of Dermatology, University of Texas, M. D. Anderson Cancer Center, Houston, Texas

Mycosis fungoides (MF) is the most common form of cutaneous T-cell lymphoma (CTCL) and arises from the accumulation and clonal proliferation of epidermotropic, CD4+/CD45RO+ (helper/memory) T lymphocytes. Loss of CD8+ CTLs within MF lesions is associated with poor prognosis and disease progression. Because T-lymphocyte apoptosis is controlled mainly through the Fas/Fas ligand (FasL) pathway and tumor cells may escape immune surveillance by expressing FasL, triggering apoptosis of tumor-infiltrating T lymphocytes, we studied the role of this system in MF. T-cell subsets, Fas/FasL expression, and apoptosis were evaluated in normal and lesional skin biopsy specimens from 21 patients with all stages of MF and in cultured CTCL cell lines (MJ, HUT78, and HH) using immunohistochemistry, terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL), and Western blotting. MF lesions and paired, clinically "normal," uninvolved skin showed increased numbers of both TUNEL-positive epidermal keratinocytes (n = 13; F = 31.146; P < 0.01, ANOVA) and dermal lymphocyte infiltrates (n = 13; F = 15.825, P < 0.01, ANOVA) compared with the normal control skin. FasL expression was highest in lesional epidermal keratinocytes, in CTCL tumor cell lines, and in dermal tumor lymphocytes in MF lesions compared with uninvolved skin. FasL colocalized with CD45RO+ cells. CD8+ cells in or adjacent to CD45RO+ cells were positively labeled by TUNEL for apoptosis. In addition, CD8+ cell numbers were decreased in areas in which FasL+ tumor cells were abundant (2.01 ± 0.86%) compared with non-FasL expressing areas (13.53 ± 3.54%; P < 0.02). These results suggest that a potential mechanism of tumor immune escape in MF is FasL-mediated apoptosis of infiltrating CD8+ CTLs.

This article has been cited by other articles:

				A. Garcia-Herrera, L. Colomo, M. Camos, J. Carreras, O. Balague, A. Martinez, A. Lopez-Guillermo, T. Estrach, and E. Campo Primary Cutaneous Small/Medium CD4+ T-Cell Lymphomas: A Heterogeneous Group of Tumors With Different Clinicopathologic Features and Outcome J. Clin. Oncol., July 10, 2008; 26(20): 3364 - 3371. [Abstract] [Full Text] [PDF]

				V. R. Fantin, A. Loboda, C. P. Paweletz, R. C. Hendrickson, J. W. Pierce, J. A. Roth, L. Li, F. Gooden, S. Korenchuk, X. S. Hou, et al. Constitutive Activation of Signal Transducers and Activators of Transcription Predicts Vorinostat Resistance in Cutaneous T-Cell Lymphoma Cancer Res., May 15, 2008; 68(10): 3785 - 3794. [Abstract] [Full Text] [PDF]

				N. Ortonne, D. Huet, C. Gaudez, A. Marie-Cardine, V. Schiavon, M. Bagot, P. Musette, and A. Bensussan Significance of circulating T-cell clones in Sezary syndrome Blood, May 15, 2006; 107(10): 4030 - 4038. [Abstract] [Full Text] [PDF]

				M. Girardi, P. W. Heald, and L. D. Wilson The Pathogenesis of Mycosis Fungoides N. Engl. J. Med., May 6, 2004; 350(19): 1978 - 1988. [Full Text] [PDF]

				X. Duan, Z. Zhou, S.-F. Jia, M. Colvin, E. A. Lafleur, and E. S. Kleinerman Interleukin-12 Enhances the Sensitivity of Human Osteosarcoma Cells to 4-Hydroperoxycyclophosphamide by a Mechanism Involving the Fas/Fas-Ligand Pathway Clin. Cancer Res., January 15, 2004; 10(2): 777 - 783. [Abstract] [Full Text] [PDF]

				G Goteri, A Filosa, B Mannello, D Stramazzotti, S Rupoli, P Leoni, and G Fabris Density of neoplastic lymphoid infiltrate, CD8+ T cells, and CD1a+ dendritic cells in mycosis fungoides J. Clin. Pathol., June 1, 2003; 56(6): 453 - 458. [Abstract] [Full Text] [PDF]

				K. L. Herne, R. Talpur, J. Breuer-McHam, R. Champlin, and M. Duvic Cytomegalovirus seropositivity is significantly associated with mycosis fungoides and Sezary syndrome Blood, March 15, 2003; 101(6): 2132 - 2135. [Abstract] [Full Text] [PDF]