| Increased natural killer cells and decreased regulatory T cells are seen in complex atypical endometrial hyperplasia and well-differentiated carcinoma treated with progestins. | |
| | |
MedLine Citation:
|
PMID: 19733383 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
Progestins are used to treat complex atypical hyperplasia and well-differentiated endometrial carcinoma in women who desire fertility preservation and those who are poor surgical candidates. Although sensitivity to progestins is thought to be associated with the presence of estrogen and progesterone receptors, it is known that receptor-negative tumors can also respond to the agent, suggesting that there is another direct antitumor action of progestin. Because tumor immune response is an additional predictor of survival in well-differentiated endometrial carcinoma, it is surprising that the role of progestins in tumor immunity has not been investigated. Regulatory T cells modulate the immune response, whereas cytotoxic T cells directly target tumor cells. In this study, we investigated the effect of progestins on regulatory T cells and cytotoxic T cells. The pre- and posttreatment endometrial samples of 15 progestin-treated patients with complex atypical hyperplasia or well-differentiated endometrial carcinoma were evaluated for therapeutic response and the presence of cytotoxic T cells and regulatory T cells. Immunohistochemical analysis was performed for FOXP3 to identify regulatory T cells and for granzyme B to identify activated cytotoxic T cells. To further characterize the cytotoxic T cell's subpopulations, we performed CD8 (cytotoxic T-cell marker) and CD56 (natural killer cells marker). Ten of 15 patients had normal morphology on follow-up endometrial samplings, and 4 patients had persistence or progression of the disease. Regulatory T-cell counts pretreatment were significantly higher in complex atypical hyperplasia and well-differentiated endometrial carcinoma than in posttreatment normal endometrium. Residual complex atypical hyperplasia and well-differentiated endometrial carcinoma present in posttreatment samples maintained high regulatory T cells and low number of cytotoxic T cells. Progestin treatment was associated with striking increase in cytotoxic T cells in areas with decidual reaction. Before treatment, most of the granzyme B+ cytotoxic T cells in complex atypical hyperplasia and well-differentiated endometrial carcinoma were CD8(+) T cells, whereas after treatment, up to 80% of cytotoxic T cells were natural killer cells. These results suggest that progestin treatment affects subpopulations of lymphocytes in the endometrium and may induce immune suppression of complex atypical hyperplasia and well-differentiated endometrial carcinoma. |
| | |
Authors:
|
Agnieszka K Witkiewicz; Thomas McConnell; Magdalena Potoczek; Robert V B Emmons; Robert J Kurman |
Related Documents
:
|
2784323 - Cytotoxic potential of anti-cd7 immunotoxin (wt1-ricin a) to purge ex vivo malignant t ... 3121223 - Cytotoxic in vitro function in the lymphoproliferative disease of granular lymphocytes. 2668413 - Interactions of plasmodium berghei sporozoites and murine kupffer cells in vitro. |
Publication Detail:
|
Type: Journal Article Date: 2009-09-04 |
Journal Detail:
|
Title: Human pathology Volume: 41 ISSN: 1532-8392 ISO Abbreviation: Hum. Pathol. Publication Date: 2010 Jan |
Date Detail:
|
Created Date: 2009-12-07 Completed Date: 2009-12-22 Revised Date: - |
Medline Journal Info:
|
Nlm Unique ID: 9421547 Medline TA: Hum Pathol Country: United States |
Other Details:
|
Languages: eng Pagination: 26-32 Citation Subset: IM |
Affiliation:
|
Department of Pathology, Thomas Jefferson University, Philadelphia, PA 19107, USA. agnieszka.witkiewicz@jefferson.edu |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Adult Antineoplastic Agents / therapeutic use* Blood Cell Count Carcinoma, Endometrioid / drug therapy*, immunology, pathology Endometrial Hyperplasia / drug therapy*, immunology, pathology Endometrial Neoplasms / drug therapy*, immunology, pathology Endometrium / drug effects, pathology Female Humans Killer Cells, Natural / immunology* Progestins / therapeutic use* T-Lymphocytes, Regulatory / immunology* |
| Chemical | |
Reg. No./Substance:
|
0/Antineoplastic Agents; 0/Progestins |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Evaluation of background exposures of Americans to dioxin-like compounds in the 1990s and the 2000s.
Next Document: Large cell change of hepatocytes in chronic viral hepatitis represents a senescent-related lesion.