Document Detail


Tumor-infiltrated immune response correlates with alterations in the apoptotic and cell cycle pathways in Hodgkin and Reed-Sternberg cells.
MedLine Citation:
PMID:  18245527     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
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:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
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:
Created Date:  2008-02-04     Completed Date:  2008-06-19     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9502500     Medline TA:  Clin Cancer Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  685-91     Citation Subset:  IM    
Affiliation:
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:
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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