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Titolo:
Fas ligand expression by neoplastic T lymphocytes mediates elimination of CD8+cytotoxic T lymphocytes in mycosis fungoides: A potential mechanism of tumor immune escape?
Autore:
Ni, X; Hazarika, P; Zhang, CL; Tapur, R; Duvic, M;
Indirizzi:
Univ Texas, MD Anderson Canc Ctr, Dept Dermatol, Houston, TX 77030 USA Univ Texas Houston TX USA 77030 Ctr, Dept Dermatol, Houston, TX 77030 USA
Titolo Testata:
CLINICAL CANCER RESEARCH
fascicolo: 9, volume: 7, anno: 2001,
pagine: 2682 - 2692
SICI:
1078-0432(200109)7:9<2682:FLEBNT>2.0.ZU;2-V
Fonte:
ISI
Lingua:
ENG
Soggetto:
PROGRAMMED CELL-DEATH; LONG-TERM SURVIVAL; SEZARY-SYNDROME; CYTOKINE PRODUCTION; CROSS-LINKING; GENE-TRANSFER; CD95 LIGAND; LYMPHOMA; APOPTOSIS; COUNTERATTACK;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Citazioni:
57
Recensione:
Indirizzi per estratti:
Indirizzo: Duvic, M Univ Texas, MD Anderson Canc Ctr, Dept Dermatol, Box 434,1515 Holcombe Blvd, Houston, TX 77030 USA Univ Texas Box 434,1515 Holcombe Blvd Houston TX USA 77030 30 USA
Citazione:
X. Ni et al., "Fas ligand expression by neoplastic T lymphocytes mediates elimination of CD8+cytotoxic T lymphocytes in mycosis fungoides: A potential mechanism of tumor immune escape?", CLIN CANC R, 7(9), 2001, pp. 2682-2692

Abstract

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 NIF 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 tumorinfiltrating T lymphocytes, we studied the role of this system in NIF. 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 (NU, HUT78, and HH) using immunohistochemistry, terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL), and Western blotting. NIF 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.

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Documento generato il 07/04/20 alle ore 23:01:32