The Fas/Fas‐ligand system: a mechanism for immune evasion in human breast carcinomas
Autor: | Frederick Naftolin, Tracy Niven-Fairchild, Linda S. Gutierrez, Gil Mor, Mariel Eliza |
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Rok vydání: | 1999 |
Předmět: |
Cancer Research
Fas Ligand Protein T-Lymphocytes Blotting Western Population Apoptosis Breast Neoplasms Biology Fas ligand Lymphocytic Infiltrate Immune system Breast cancer Tumor Cells Cultured medicine Humans Neoplastic transformation RNA Messenger fas Receptor skin and connective tissue diseases education education.field_of_study Membrane Glycoproteins Reverse Transcriptase Polymerase Chain Reaction Tumor-infiltrating lymphocytes medicine.disease Clone Cells Oncology Cancer research Breast carcinoma Cell Division |
Zdroj: | Breast Cancer Research and Treatment. 54:245-253 |
ISSN: | 1573-7217 0167-6806 |
DOI: | 10.1023/a:1006102601215 |
Popis: | Breast tumors are frequently associated with a predominantly lymphocytic infiltrate, which constitutes an immune response against the tumor. In spite of this massive infiltrate, the immune response appears to be inefficient and the tumor is able to evade it. We propose that in breast cancer, tumor escape from immunological surveillance results from the induction of apoptosis of Fas-bearing activated lymphocytes by FasL-bearing breast cancer cells. To test this proposal we studied the expression of FasL by human breast carcinomas and the MCF-7 breast cancer cell line by RT-PCR, immunohistochemistry, and Western Blot. Moreover, we describe the presence of apoptosis and Fas expression in the lymphocytic population surrounding the tumor. Strong membranous and cytoplasmic staining was detected in ductal carcinomas and hyperplastic breast tissue, but it was absent from normal breast tissue. No staining was found in normal glands in the non-tumor quadrants; however, the normal appearing ducts surrounding the carcinoma (tumor quadrant) showed intense immunoreactivity. Apoptosis was found predominantly among the lymphocytic population, as well as in the blood vessels and fibro-fatty tissue close to the tumor. Further characterization of apoptotic cells demonstrated that they were CD3+ cells. Our results suggest the breast tumors may elude immunological surveillance by inducing, via the Fas/FasL system, the apoptosis of activated lymphocytes. Recent data have demonstrated FasL RNA in other tumor types. Upregulation of FasL expression in hyperplastic and normal breast ducts close to the tumor also suggests a possible role in early neoplastic transformation and proliferation. |
Databáze: | OpenAIRE |
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