Document Detail


Radiation-induced loss of cell surface CD47 enhances immune-mediated clearance of human papillomavirus-positive cancer.
MedLine Citation:
PMID:  23292955     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The increasing incidence of human papillomavirus (HPV) related oropharyngeal squamous cell carcinoma (OSSC) demands development of novel therapies. Despite presenting at a more advanced stage, HPV(+) oropharyngeal squamous cell carcinoma (OSCC) have a better prognosis than their HPV(-) counterparts. We have previously demonstrated that clearance of HPV(+) OSCC during treatment with radiation and chemotherapy requires an immune response which is likely responsible for the improved clinical outcomes. To further elucidate the mechanism of immune-mediated clearance, we asked whether radiation therapy induces tumor cell changes that allow the body to recognize and aid in tumor clearance. Here, we describe a radiation-induced change in tumor surface protein expression that is critical for immune-mediated clearance. Radiation therapy decreases surface expression of CD47, a self-marker. CD47 is frequently overexpressed in head and neck squamous cell carcinoma and radiation induces a decrease of CD47 in a dose-dependent manner. We show that both in vitro and in vivo tumor cell CD47 protein levels are restored over time after sublethal radiation exposure and that protein levels on adjacent, normal tissues remain unaffected. Furthermore, reduction of tumor cell CD47 increases phagocytosis of these cells by dendritic cells and leads to increased interferon gamma and granzyme production from mixed lymphocytes. Finally, decreasing tumor cell CD47 in combination with standard radiation and chemotherapy results in improved immune-mediated tumor clearance in vivo. These findings help define an important mechanism of radiation-related immune clearance and suggest that decreasing CD47 specifically on tumor cells may be a good therapeutic target for HPV related disease.
Authors:
Daniel W Vermeer; William C Spanos; Paola D Vermeer; Annie M Bruns; Kimberly M Lee; John H Lee
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2013-02-12
Journal Detail:
Title:  International journal of cancer. Journal international du cancer     Volume:  133     ISSN:  1097-0215     ISO Abbreviation:  Int. J. Cancer     Publication Date:  2013 Jul 
Date Detail:
Created Date:  2013-04-22     Completed Date:  2013-06-11     Revised Date:  2014-04-08    
Medline Journal Info:
Nlm Unique ID:  0042124     Medline TA:  Int J Cancer     Country:  United States    
Other Details:
Languages:  eng     Pagination:  120-9     Citation Subset:  IM    
Copyright Information:
Copyright © 2013 UICC.
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MeSH Terms
Descriptor/Qualifier:
Animals
Antigens, CD47 / immunology*
Antineoplastic Agents / therapeutic use
Carcinoma, Squamous Cell / immunology*,  radiotherapy*,  virology
Cell Line, Tumor
Cell Survival
Cisplatin / therapeutic use
Dose-Response Relationship, Radiation
Granzymes / immunology
Human papillomavirus 16* / isolation & purification
Humans
Interferon-gamma / immunology
Male
Mice
Oropharyngeal Neoplasms / immunology*,  radiotherapy*,  virology
Papillomavirus Infections / complications*
Phagocytosis
Radiotherapy, Adjuvant
Grant Support
ID/Acronym/Agency:
1P20RR024219-01A2/RR/NCRR NIH HHS; 5P20RR017662-08/RR/NCRR NIH HHS; 7R01DE018386-03/DE/NIDCR NIH HHS; P20 GM103548/GM/NIGMS NIH HHS; R01 DE018386/DE/NIDCR NIH HHS
Chemical
Reg. No./Substance:
0/Antigens, CD47; 0/Antineoplastic Agents; 0/CD47 protein, human; 0/Cd47 protein, mouse; 82115-62-6/Interferon-gamma; EC 3.4.21.-/Granzymes; Q20Q21Q62J/Cisplatin

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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