The Fas counterattack in vivo: apoptotic depletion of tumor-infiltrating lymphocytes associated with Fas ligand expression by human esophageal carcinoma.

Hdl Handle:
http://hdl.handle.net/10147/209189
Title:
The Fas counterattack in vivo: apoptotic depletion of tumor-infiltrating lymphocytes associated with Fas ligand expression by human esophageal carcinoma.
Authors:
Bennett, M W; O'Connell, J; O'Sullivan, G C; Brady, C; Roche, D; Collins, J K; Shanahan, F
Affiliation:
Department of Medicine, Cork University Hospital, Ireland.
Citation:
J Immunol. 1998 Jun 1;160(11):5669-75.
Journal:
Journal of immunology (Baltimore, Md. : 1950)
Issue Date:
3-Feb-2012
URI:
http://hdl.handle.net/10147/209189
PubMed ID:
9605174
Abstract:
Various cancer cell lines express Fas ligand (FasL) and can kill lymphoid cells by Fas-mediated apoptosis in vitro. FasL expression has been demonstrated in several human malignancies in vivo. We sought to determine whether human esophageal carcinomas express FasL, and whether FasL expression is associated with increased apoptosis of tumor-infiltrating lymphocytes (TIL) in vivo, thereby contributing to the immune privilege of the tumor. Using in situ hybridization and immunohistochemistry, respectively, FasL mRNA and protein were colocalized to neoplastic esophageal epithelial cells in all esophageal carcinomas (squamous, n = 6; adenocarcinoma, n = 2). The Extent of FasL expression was variable, with both FasL-positive and FasL-negative neoplastic regions occurring within tumors. TIL were detected by immunohistochemical staining for the leukocyte common Ag, CD45. FasL expression was associated with a mean fourfold depletion of TIL when compared with FasL-negative areas within the same tumors (range 1.6- to 12-fold, n = 6,p < 0.05). Cell death of TIL was detected by dual staining of CD45 (immunohistochemistry) and DNA strand breaks (TUNEL, terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling). There was a mean twofold increase in detectable cell death among TIL in FasL-positive areas compared with FasL-negative areas (range 1.6- to 2.4-fold, n = 6, p < 0.05). In conclusion, we demonstrate a statistically significant, quantitative reduction of TIL concomitant with significantly increased TIL apoptosis within FasL-expressing areas of esophageal tumors. Our findings suggest Fas-mediated apoptotic depletion of TIL in response to FasL expression by esophageal cancers, and provide the first direct, quantitative evidence to support the Fas counterattack as a mechanism of immune privilege in vivo in human cancer.
Language:
eng
MeSH:
Adenocarcinoma/*immunology/metabolism/pathology; Antigens, CD95/*metabolism; Apoptosis/*immunology; Carcinoma, Squamous Cell/*immunology/metabolism/pathology; Esophageal Neoplasms/*immunology/metabolism/pathology; Fas Ligand Protein; Humans; Immunohistochemistry; Ligands; *Lymphocyte Depletion; Lymphocytes, Tumor-Infiltrating/*immunology/pathology; Membrane Glycoproteins/*biosynthesis
ISSN:
0022-1767 (Print); 0022-1767 (Linking)

Full metadata record

DC FieldValue Language
dc.contributor.authorBennett, M Wen_GB
dc.contributor.authorO'Connell, Jen_GB
dc.contributor.authorO'Sullivan, G Cen_GB
dc.contributor.authorBrady, Cen_GB
dc.contributor.authorRoche, Den_GB
dc.contributor.authorCollins, J Ken_GB
dc.contributor.authorShanahan, Fen_GB
dc.date.accessioned2012-02-03T15:14:37Z-
dc.date.available2012-02-03T15:14:37Z-
dc.date.issued2012-02-03T15:14:37Z-
dc.identifier.citationJ Immunol. 1998 Jun 1;160(11):5669-75.en_GB
dc.identifier.issn0022-1767 (Print)en_GB
dc.identifier.issn0022-1767 (Linking)en_GB
dc.identifier.pmid9605174en_GB
dc.identifier.urihttp://hdl.handle.net/10147/209189-
dc.description.abstractVarious cancer cell lines express Fas ligand (FasL) and can kill lymphoid cells by Fas-mediated apoptosis in vitro. FasL expression has been demonstrated in several human malignancies in vivo. We sought to determine whether human esophageal carcinomas express FasL, and whether FasL expression is associated with increased apoptosis of tumor-infiltrating lymphocytes (TIL) in vivo, thereby contributing to the immune privilege of the tumor. Using in situ hybridization and immunohistochemistry, respectively, FasL mRNA and protein were colocalized to neoplastic esophageal epithelial cells in all esophageal carcinomas (squamous, n = 6; adenocarcinoma, n = 2). The Extent of FasL expression was variable, with both FasL-positive and FasL-negative neoplastic regions occurring within tumors. TIL were detected by immunohistochemical staining for the leukocyte common Ag, CD45. FasL expression was associated with a mean fourfold depletion of TIL when compared with FasL-negative areas within the same tumors (range 1.6- to 12-fold, n = 6,p < 0.05). Cell death of TIL was detected by dual staining of CD45 (immunohistochemistry) and DNA strand breaks (TUNEL, terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling). There was a mean twofold increase in detectable cell death among TIL in FasL-positive areas compared with FasL-negative areas (range 1.6- to 2.4-fold, n = 6, p < 0.05). In conclusion, we demonstrate a statistically significant, quantitative reduction of TIL concomitant with significantly increased TIL apoptosis within FasL-expressing areas of esophageal tumors. Our findings suggest Fas-mediated apoptotic depletion of TIL in response to FasL expression by esophageal cancers, and provide the first direct, quantitative evidence to support the Fas counterattack as a mechanism of immune privilege in vivo in human cancer.en_GB
dc.language.isoengen_GB
dc.subject.meshAdenocarcinoma/*immunology/metabolism/pathologyen_GB
dc.subject.meshAntigens, CD95/*metabolismen_GB
dc.subject.meshApoptosis/*immunologyen_GB
dc.subject.meshCarcinoma, Squamous Cell/*immunology/metabolism/pathologyen_GB
dc.subject.meshEsophageal Neoplasms/*immunology/metabolism/pathologyen_GB
dc.subject.meshFas Ligand Proteinen_GB
dc.subject.meshHumansen_GB
dc.subject.meshImmunohistochemistryen_GB
dc.subject.meshLigandsen_GB
dc.subject.mesh*Lymphocyte Depletionen_GB
dc.subject.meshLymphocytes, Tumor-Infiltrating/*immunology/pathologyen_GB
dc.subject.meshMembrane Glycoproteins/*biosynthesisen_GB
dc.titleThe Fas counterattack in vivo: apoptotic depletion of tumor-infiltrating lymphocytes associated with Fas ligand expression by human esophageal carcinoma.en_GB
dc.contributor.departmentDepartment of Medicine, Cork University Hospital, Ireland.en_GB
dc.identifier.journalJournal of immunology (Baltimore, Md. : 1950)en_GB
dc.description.provinceMunster-

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