Linked Life Data

20145137

Source:http://linkedlifedata.com/resource/pubmed/id/20145137

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2010-2-16
pubmed:abstractText
Antiestrogens are universally used to treat estrogen receptor--positive breast cancer, but relapses occur commonly due to the development of drug resistance. The ability of antiestrogen to induce transforming growth factor beta (TGFbeta) in breast cancer cells may be relevant to the emergence of resistance, not only at the level of cell autonomous effects of TGFbeta on cancer progression but also at the level of its effects on the host immune system. To evaluate the potential role of tumor-derived, antiestrogen-induced TGFbeta as an immune suppressor, we established in vitro mixed lymphocyte tumor reactions (MLTR) using MCF-7 cells and peripheral blood mononuclear cells (PBMC), as well as tumor tissue and autologous tumor infiltrating lymphocytes (TIL) obtained from primary breast cancer biopsies. In allogeneic MLTR, antiestrogen-treated MCF-7 cells caused downregulation of the effector molecules granzyme B, perforin, and Fas ligand in CD8(+) T cells, and suppressed the generation of cytotoxic effector cells in a TGFbeta-dependent manner. Furthermore, we documented induction of regulatory T cells in CD4(+) T cells, based on Foxp3 expression and T-cell activation in cocultures. In autologous MLTR, antiestrogen treatment gave rise to enhanced Foxp3 expression of TIL/PBMC and decreased the number of apoptotic tumor cells. These effects were reversed by addition of a TGFbeta neutralizing antibody. Our findings offer evidence that antiestrogen induces immunosuppression in the tumor microenvironment, through a TGFbeta-dependent mechanism that may contribute to the development of antiestrogen resistance in breast cancer.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
1538-7445
pubmed:author
pubmed:issnType
Electronic
pubmed:day
15
pubmed:volume
70
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1314-22
pubmed:meshHeading
pubmed-meshheading:20145137-Antineoplastic Agents, Hormonal, pubmed-meshheading:20145137-Breast Neoplasms, pubmed-meshheading:20145137-CD8-Positive T-Lymphocytes, pubmed-meshheading:20145137-Carcinoma, pubmed-meshheading:20145137-Cell Line, Tumor, pubmed-meshheading:20145137-Cells, Cultured, pubmed-meshheading:20145137-Coculture Techniques, pubmed-meshheading:20145137-Drug Resistance, Neoplasm, pubmed-meshheading:20145137-Drug Synergism, pubmed-meshheading:20145137-Estradiol, pubmed-meshheading:20145137-Estrogen Receptor Modulators, pubmed-meshheading:20145137-Female, pubmed-meshheading:20145137-Forkhead Transcription Factors, pubmed-meshheading:20145137-Gene Expression Regulation, Neoplastic, pubmed-meshheading:20145137-Humans, pubmed-meshheading:20145137-Immune Tolerance, pubmed-meshheading:20145137-Tamoxifen, pubmed-meshheading:20145137-Transforming Growth Factor beta
pubmed:year
2010
pubmed:articleTitle
Antiestrogens induce transforming growth factor beta-mediated immunosuppression in breast cancer.
pubmed:affiliation
Robert Bosch Hospital, Department of Clinical Chemistry, Dr. Margarete Fischer-Bosch-Institute of Clinical Pharmacology and Institute of Cell Biology and Immunology, University of Stuttgart, Auerbachstr 112, Stuttgart, Germany. christian.joffroy@ikp-stuttgart.de
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't