Document Detail


Altered local and systemic immune profiles underlie lymph node metastasis in breast cancer patients.
MedLine Citation:
PMID:  23136075     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Cancer-mediated immune dysfunction contributes to tumor progression and correlates with patient outcome. Metastasis to tumor draining lymph nodes (TDLNs) is an important step in breast cancer progression and is used to predict patient outcome and survival. Although lymph nodes are important immune organs, the role of immune cells in TDLNs has not been thoroughly investigated. We hypothesized that the host immune response in node negative (NN) patients is more intact and thereby can resist tumor invasion compared to node positive (NP) patients. As such, lymph node metastasis requires breakdown of the host immune response in addition to escape of cancer cells from the tumor. To investigate the immunological differences between NN and NP breast cancer patients, we purified and profiled immune cells from the three major compartments where cancer and immune cells interact: tumor, TDLNs and peripheral blood. Significant down-regulation of genes associated with immune-related pathways and up-regulation of genes associated with tumor-promoting pathways was consistently observed in NP patients' TDLNs compared to NN patients. Importantly, these signatures were seen even in NP patients' tumor-free TDLNs, suggesting that such immune changes are not driven solely by local tumor invasion. Furthermore, similar patterns were also observed in NP patients' tumor and blood immune cells, suggesting that immunological differences between NN and NP patients are systemic. Together, these findings suggest that alterations in overall immune function may underlie risk for LN metastasis in breast cancer patients.
Authors:
Neta S Zuckerman; Hongxiang Yu; Diana L Simons; Nupur Bhattacharya; Valeria Carcamo-Cavazos; Ning Yan; Frederick M Dirbas; Denise L Johnson; Erich J Schwartz; Peter P Lee
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, Non-P.H.S.     Date:  2012-11-26
Journal Detail:
Title:  International journal of cancer. Journal international du cancer     Volume:  132     ISSN:  1097-0215     ISO Abbreviation:  Int. J. Cancer     Publication Date:  2013 Jun 
Date Detail:
Created Date:  2013-03-26     Completed Date:  2013-05-28     Revised Date:  2014-06-03    
Medline Journal Info:
Nlm Unique ID:  0042124     Medline TA:  Int J Cancer     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2537-47     Citation Subset:  IM    
Copyright Information:
Copyright © 2012 UICC.
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MeSH Terms
Descriptor/Qualifier:
Breast Neoplasms / genetics,  immunology,  pathology*
Female
Follow-Up Studies
Gene Expression Profiling*
Humans
Lymph Nodes / pathology*
Lymphatic Metastasis
Middle Aged
Oligonucleotide Array Sequence Analysis
Prognosis
RNA, Messenger / genetics
Real-Time Polymerase Chain Reaction
Reverse Transcriptase Polymerase Chain Reaction
Sentinel Lymph Node Biopsy
Tumor Markers, Biological / genetics*,  immunology
Grant Support
ID/Acronym/Agency:
P30 CA124435/CA/NCI NIH HHS; R01 CA127947/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
0/RNA, Messenger; 0/Tumor Markers, Biological
Comments/Corrections

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