Fas ligand expression by neoplastic T lymphocytes mediates elimination of CD8+ cytotoxic T lymphocytes in mycosis fungoides : A potential mechanism of tumor immune escape?
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. B...
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Veröffentlicht in: | Clinical cancer research 2001-09, Vol.7 (9), p.2682-2692 |
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description | 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. |
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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.</description><identifier>ISSN: 1078-0432</identifier><identifier>EISSN: 1557-3265</identifier><identifier>PMID: 11555580</identifier><language>eng</language><publisher>Philadelphia, PA: American Association for Cancer Research</publisher><subject>Adult ; Aged ; Apoptosis ; Biological and medical sciences ; CD8 Antigens - metabolism ; Fas Ligand Protein ; Female ; General aspects (metabolism, cell proliferation, established cell line...) ; Humans ; Immunohistochemistry ; In Situ Nick-End Labeling ; Jurkat Cells ; Leukocyte Common Antigens - metabolism ; Male ; Medical sciences ; Membrane Glycoproteins - biosynthesis ; Middle Aged ; Mycosis Fungoides - immunology ; Mycosis Fungoides - metabolism ; Mycosis Fungoides - pathology ; Skin - chemistry ; Skin - immunology ; Skin - pathology ; Skin Neoplasms - immunology ; Skin Neoplasms - metabolism ; Skin Neoplasms - pathology ; T-Lymphocytes - chemistry ; T-Lymphocytes - immunology ; T-Lymphocytes - pathology ; T-Lymphocytes, Cytotoxic - immunology ; T-Lymphocytes, Cytotoxic - metabolism ; T-Lymphocytes, Cytotoxic - pathology ; Tumor cell ; Tumor Cells, Cultured ; Tumors</subject><ispartof>Clinical cancer research, 2001-09, Vol.7 (9), p.2682-2692</ispartof><rights>2001 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>315,781,785</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=1137430$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/11555580$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>XIAO NI</creatorcontrib><creatorcontrib>HAZARIKA, Parul</creatorcontrib><creatorcontrib>CHUNLEI ZHANG</creatorcontrib><creatorcontrib>TALPUR, Rakhashandra</creatorcontrib><creatorcontrib>DUVIC, Madeleine</creatorcontrib><title>Fas ligand expression by neoplastic T lymphocytes mediates elimination of CD8+ cytotoxic T lymphocytes in mycosis fungoides : A potential mechanism of tumor immune escape?</title><title>Clinical cancer research</title><addtitle>Clin Cancer Res</addtitle><description>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.</description><subject>Adult</subject><subject>Aged</subject><subject>Apoptosis</subject><subject>Biological and medical sciences</subject><subject>CD8 Antigens - metabolism</subject><subject>Fas Ligand Protein</subject><subject>Female</subject><subject>General aspects (metabolism, cell proliferation, established cell line...)</subject><subject>Humans</subject><subject>Immunohistochemistry</subject><subject>In Situ Nick-End Labeling</subject><subject>Jurkat Cells</subject><subject>Leukocyte Common Antigens - metabolism</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Membrane Glycoproteins - biosynthesis</subject><subject>Middle Aged</subject><subject>Mycosis Fungoides - immunology</subject><subject>Mycosis Fungoides - metabolism</subject><subject>Mycosis Fungoides - pathology</subject><subject>Skin - chemistry</subject><subject>Skin - immunology</subject><subject>Skin - pathology</subject><subject>Skin Neoplasms - immunology</subject><subject>Skin Neoplasms - metabolism</subject><subject>Skin Neoplasms - pathology</subject><subject>T-Lymphocytes - chemistry</subject><subject>T-Lymphocytes - immunology</subject><subject>T-Lymphocytes - pathology</subject><subject>T-Lymphocytes, Cytotoxic - immunology</subject><subject>T-Lymphocytes, Cytotoxic - metabolism</subject><subject>T-Lymphocytes, Cytotoxic - pathology</subject><subject>Tumor cell</subject><subject>Tumor Cells, Cultured</subject><subject>Tumors</subject><issn>1078-0432</issn><issn>1557-3265</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2001</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNplkF9LwzAUxYsobk6_guRBfJFC0rRp6ouM6VQY-DKfR5rebpH8qU0K62fyS5rhBMH7cg-X3zlwz0kyJUVRpjRjxWnUuOQpzmk2SS68_8CY5ATn58mERKooOJ4mX0vhkVZbYRsE-64H75WzqB6RBddp4YOSaI30aLqdk2MAjww0ShwEaGWUFeFgcC1aPPI7FBEX3P6fSVlkRum88qgd7NapJh7v0Rx1LoANSuiYK3fCKm8OYWEwrkfKmMECAi9FBw-XyVkrtIer454l78un9eIlXb09vy7mq7TLKAspKcq6zTDPGeOMCy6BV5gx2rCyikMrLireNKzlIAWpa86A0RaTuspKDnlGZ8ntT27Xu88BfNgY5SVoLWIng9-UhLAqw2UEr4_gUMdWNl2vjOjHzW-9Ebg5AiK-oNteWKn8H46WOcX0G7zRhvM</recordid><startdate>20010901</startdate><enddate>20010901</enddate><creator>XIAO NI</creator><creator>HAZARIKA, Parul</creator><creator>CHUNLEI ZHANG</creator><creator>TALPUR, Rakhashandra</creator><creator>DUVIC, Madeleine</creator><general>American Association for Cancer Research</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>7X8</scope></search><sort><creationdate>20010901</creationdate><title>Fas ligand expression by neoplastic T lymphocytes mediates elimination of CD8+ cytotoxic T lymphocytes in mycosis fungoides : A potential mechanism of tumor immune escape?</title><author>XIAO NI ; HAZARIKA, Parul ; CHUNLEI ZHANG ; TALPUR, Rakhashandra ; DUVIC, Madeleine</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-p236t-157bf208466868a8ce890663d679999398a98dd6f8eca1bb86e63f01b9278e423</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2001</creationdate><topic>Adult</topic><topic>Aged</topic><topic>Apoptosis</topic><topic>Biological and medical sciences</topic><topic>CD8 Antigens - metabolism</topic><topic>Fas Ligand Protein</topic><topic>Female</topic><topic>General aspects (metabolism, cell proliferation, established cell line...)</topic><topic>Humans</topic><topic>Immunohistochemistry</topic><topic>In Situ Nick-End Labeling</topic><topic>Jurkat Cells</topic><topic>Leukocyte Common Antigens - metabolism</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Membrane Glycoproteins - biosynthesis</topic><topic>Middle Aged</topic><topic>Mycosis Fungoides - immunology</topic><topic>Mycosis Fungoides - metabolism</topic><topic>Mycosis Fungoides - pathology</topic><topic>Skin - chemistry</topic><topic>Skin - immunology</topic><topic>Skin - pathology</topic><topic>Skin Neoplasms - immunology</topic><topic>Skin Neoplasms - metabolism</topic><topic>Skin Neoplasms - pathology</topic><topic>T-Lymphocytes - chemistry</topic><topic>T-Lymphocytes - immunology</topic><topic>T-Lymphocytes - pathology</topic><topic>T-Lymphocytes, Cytotoxic - immunology</topic><topic>T-Lymphocytes, Cytotoxic - metabolism</topic><topic>T-Lymphocytes, Cytotoxic - pathology</topic><topic>Tumor cell</topic><topic>Tumor Cells, Cultured</topic><topic>Tumors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>XIAO NI</creatorcontrib><creatorcontrib>HAZARIKA, Parul</creatorcontrib><creatorcontrib>CHUNLEI ZHANG</creatorcontrib><creatorcontrib>TALPUR, Rakhashandra</creatorcontrib><creatorcontrib>DUVIC, Madeleine</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>MEDLINE - Academic</collection><jtitle>Clinical cancer research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>XIAO NI</au><au>HAZARIKA, Parul</au><au>CHUNLEI ZHANG</au><au>TALPUR, Rakhashandra</au><au>DUVIC, Madeleine</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Fas ligand expression by neoplastic T lymphocytes mediates elimination of CD8+ cytotoxic T lymphocytes in mycosis fungoides : A potential mechanism of tumor immune escape?</atitle><jtitle>Clinical cancer research</jtitle><addtitle>Clin Cancer Res</addtitle><date>2001-09-01</date><risdate>2001</risdate><volume>7</volume><issue>9</issue><spage>2682</spage><epage>2692</epage><pages>2682-2692</pages><issn>1078-0432</issn><eissn>1557-3265</eissn><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 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.</abstract><cop>Philadelphia, PA</cop><pub>American Association for Cancer Research</pub><pmid>11555580</pmid><tpages>11</tpages></addata></record> |
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subjects | Adult Aged Apoptosis Biological and medical sciences CD8 Antigens - metabolism Fas Ligand Protein Female General aspects (metabolism, cell proliferation, established cell line...) Humans Immunohistochemistry In Situ Nick-End Labeling Jurkat Cells Leukocyte Common Antigens - metabolism Male Medical sciences Membrane Glycoproteins - biosynthesis Middle Aged Mycosis Fungoides - immunology Mycosis Fungoides - metabolism Mycosis Fungoides - pathology Skin - chemistry Skin - immunology Skin - pathology Skin Neoplasms - immunology Skin Neoplasms - metabolism Skin Neoplasms - pathology T-Lymphocytes - chemistry T-Lymphocytes - immunology T-Lymphocytes - pathology T-Lymphocytes, Cytotoxic - immunology T-Lymphocytes, Cytotoxic - metabolism T-Lymphocytes, Cytotoxic - pathology Tumor cell Tumor Cells, Cultured Tumors |
title | Fas ligand expression by neoplastic T lymphocytes mediates elimination of CD8+ cytotoxic T lymphocytes in mycosis fungoides : A potential mechanism of tumor immune escape? |
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