| Tumor-infiltrated immune response correlates with alterations in the apoptotic and cell cycle pathways in Hodgkin and Reed-Sternberg cells. | |
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MedLine Citation:
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PMID: 18245527 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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PURPOSE: To analyze tumor-microenvironment relationships in Hodgkin lymphoma (HL) as potential determinants in the decision-making process related to the alterations in cell cycle and apoptotic pathways of Hodgkin/Reed-Sternberg (H/RS) cells. EXPERIMENTAL DESIGN: Based on a cohort of 257 classic HL patients, we carried out a global descriptive correlational analysis and logistic regression study to identify tumor-infiltrated immune cell rate in HL that could be interconnected with genes involved in the regulation of apoptotic/proliferative pathways in H/RS cells. RESULTS: Our results reveal the existence of a connection between the reactive microenvironment and molecular changes in apoptotic/proliferative pathways in H/RS cells. A lesser incidence of infiltrated cytotoxic cells in the tumor (CD8(+) T lymphocytes, CD57(+) natural killer, and granzyme B(+) cells) was associated with overexpression of antiapoptotic proteins (Bcl-X(L), survivin, caspase-3, and nuclear factor-kappaB) in tumoral cells. Increased incidence of general infiltrated immune cells, such as CD4(+) T lymphocytes, CD57(+) natural killer cells, activated CTL, and dendritic cells, in the microenvironment of the tumor was associated with increased growth fraction of tumoral cells, including G(1)-S checkpoint (cyclin D and cyclin E) and tumor suppressor pathways (p16 and SKP2), and with the presence of EBV (signal transducers and activators of transcription 1 and 3 expression; STAT1/STAT3). CONCLUSIONS: A lower level of cytotoxic cells correlated with an increase of antiapoptotic mechanisms in H/RS cells, whereas the global infiltrated immune population correlated with the growth fraction of the tumor. Our collective data suggest a causal relationship between infiltrated immune response and concurrent changes of the different proliferative checkpoints, tumor suppressor, and apoptotic pathways of H/RS cells in HL. |
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Authors:
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Tomás Alvaro; Marylène Lejeune; Juan F García; Ma Teresa Salvadó; Carlos López; Ramón Bosch; Joaquín Jaén; Patricia Escrivá; Lluis E Pons |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Clinical cancer research : an official journal of the American Association for Cancer Research Volume: 14 ISSN: 1078-0432 ISO Abbreviation: Clin. Cancer Res. Publication Date: 2008 Feb |
Date Detail:
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Created Date: 2008-02-04 Completed Date: 2008-06-19 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 9502500 Medline TA: Clin Cancer Res Country: United States |
Other Details:
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Languages: eng Pagination: 685-91 Citation Subset: IM |
Affiliation:
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Department of Pathology, Hospital de Tortosa Verge de la Cinta, Tortosa, Spain. talvaro.htvc.ics@gencat.net |
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| MeSH Terms | |
Descriptor/Qualifier:
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Apoptosis* Cell Cycle* Dendritic Cells / pathology Hodgkin Disease / immunology, pathology* Humans Immunohistochemistry In Situ Hybridization Killer Cells, Natural / pathology Lymphocytes, Tumor-Infiltrating / pathology Reed-Sternberg Cells / immunology, pathology* Regression Analysis T-Lymphocytes / pathology |
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