Expression of Fas (CD95/APO-1) ligand by human breast cancers: significance for tumor immune privilege.

Hdl Handle:
http://hdl.handle.net/10147/209149
Title:
Expression of Fas (CD95/APO-1) ligand by human breast cancers: significance for tumor immune privilege.
Authors:
O'Connell, J; Bennett, M W; O'Sullivan, G C; O'Callaghan, J; Collins, J K; Shanahan, F
Affiliation:
Department of Medicine, Cork University Hospital, National University of Ireland,, Cork, Ireland.
Citation:
Clin Diagn Lab Immunol. 1999 Jul;6(4):457-63.
Journal:
Clinical and diagnostic laboratory immunology
Issue Date:
3-Feb-2012
URI:
http://hdl.handle.net/10147/209149
PubMed ID:
10391843
Abstract:
Breast cancers have been shown to elicit tumor-specific immune responses. As in other types of cancer, the antitumor immune response fails to contain breast tumor growth, and a reduction in both the quantity and cytotoxic effectiveness of tumor-infiltrating lymphocytes (TILs) is associated with a poorer prognosis. Fas ligand (FasL) induces apoptotic death of activated lymphocytes that express its cell surface receptor, FasR (CD95/APO-1). FasL-mediated apoptosis of activated lymphocytes contributes to normal immune downregulation through its roles in tolerance acquisition, immune response termination, and maintenance of immune privilege in the eye, testis, and fetus. In this report, we demonstrate that breast carcinomas express FasL. Using in situ hybridization and immunohistochemistry, we show that breast tumors constitutively express FasL at both the mRNA and protein levels, respectively. FasL expression is prevalent in breast cancer: 100% of breast tumors (17 of 17) were found to express FasL, and expression occurred over more than 50% of the tumor area in all cases. By immunohistochemistry, FasR was found to be coexpressed with FasL throughout large areas of all the breast tumors. This suggests that the tumor cells had acquired intracellular defects in FasL-mediated apoptotic signaling. FasL and FasR expression were independent of tumor type or infiltrative capacity. FasL expressed by tumor cells has previously been shown to kill Fas-sensitive lymphoid cells in vitro and has been associated with apoptosis of TILs in vivo. We conclude that mammary carcinomas express FasL in vivo as a potential inhibitor of the antitumor immune response.
Language:
eng
MeSH:
Antigens, CD95/biosynthesis; Breast Neoplasms/*chemistry/pathology; Fas Ligand Protein; Female; Humans; Immunoblotting; Immunohistochemistry; Lymphocytes/chemistry; Lymphocytes, Tumor-Infiltrating/chemistry; Membrane Glycoproteins/*genetics; Neurons/chemistry; RNA, Messenger/analysis; Receptors, Tumor Necrosis Factor/biosynthesis; Reverse Transcriptase Polymerase Chain Reaction
ISSN:
1071-412X (Print); 1071-412X (Linking)

Full metadata record

DC FieldValue Language
dc.contributor.authorO'Connell, Jen_GB
dc.contributor.authorBennett, M Wen_GB
dc.contributor.authorO'Sullivan, G Cen_GB
dc.contributor.authorO'Callaghan, Jen_GB
dc.contributor.authorCollins, J Ken_GB
dc.contributor.authorShanahan, Fen_GB
dc.date.accessioned2012-02-03T15:13:33Z-
dc.date.available2012-02-03T15:13:33Z-
dc.date.issued2012-02-03T15:13:33Z-
dc.identifier.citationClin Diagn Lab Immunol. 1999 Jul;6(4):457-63.en_GB
dc.identifier.issn1071-412X (Print)en_GB
dc.identifier.issn1071-412X (Linking)en_GB
dc.identifier.pmid10391843en_GB
dc.identifier.urihttp://hdl.handle.net/10147/209149-
dc.description.abstractBreast cancers have been shown to elicit tumor-specific immune responses. As in other types of cancer, the antitumor immune response fails to contain breast tumor growth, and a reduction in both the quantity and cytotoxic effectiveness of tumor-infiltrating lymphocytes (TILs) is associated with a poorer prognosis. Fas ligand (FasL) induces apoptotic death of activated lymphocytes that express its cell surface receptor, FasR (CD95/APO-1). FasL-mediated apoptosis of activated lymphocytes contributes to normal immune downregulation through its roles in tolerance acquisition, immune response termination, and maintenance of immune privilege in the eye, testis, and fetus. In this report, we demonstrate that breast carcinomas express FasL. Using in situ hybridization and immunohistochemistry, we show that breast tumors constitutively express FasL at both the mRNA and protein levels, respectively. FasL expression is prevalent in breast cancer: 100% of breast tumors (17 of 17) were found to express FasL, and expression occurred over more than 50% of the tumor area in all cases. By immunohistochemistry, FasR was found to be coexpressed with FasL throughout large areas of all the breast tumors. This suggests that the tumor cells had acquired intracellular defects in FasL-mediated apoptotic signaling. FasL and FasR expression were independent of tumor type or infiltrative capacity. FasL expressed by tumor cells has previously been shown to kill Fas-sensitive lymphoid cells in vitro and has been associated with apoptosis of TILs in vivo. We conclude that mammary carcinomas express FasL in vivo as a potential inhibitor of the antitumor immune response.en_GB
dc.language.isoengen_GB
dc.subject.meshAntigens, CD95/biosynthesisen_GB
dc.subject.meshBreast Neoplasms/*chemistry/pathologyen_GB
dc.subject.meshFas Ligand Proteinen_GB
dc.subject.meshFemaleen_GB
dc.subject.meshHumansen_GB
dc.subject.meshImmunoblottingen_GB
dc.subject.meshImmunohistochemistryen_GB
dc.subject.meshLymphocytes/chemistryen_GB
dc.subject.meshLymphocytes, Tumor-Infiltrating/chemistryen_GB
dc.subject.meshMembrane Glycoproteins/*geneticsen_GB
dc.subject.meshNeurons/chemistryen_GB
dc.subject.meshRNA, Messenger/analysisen_GB
dc.subject.meshReceptors, Tumor Necrosis Factor/biosynthesisen_GB
dc.subject.meshReverse Transcriptase Polymerase Chain Reactionen_GB
dc.titleExpression of Fas (CD95/APO-1) ligand by human breast cancers: significance for tumor immune privilege.en_GB
dc.contributor.departmentDepartment of Medicine, Cork University Hospital, National University of Ireland,, Cork, Ireland.en_GB
dc.identifier.journalClinical and diagnostic laboratory immunologyen_GB
dc.description.provinceMunster-

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