Document Detail


CD73 has distinct roles in nonhematopoietic and hematopoietic cells to promote tumor growth in mice.
MedLine Citation:
PMID:  21537079     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
CD73 is overexpressed in many types of human and mouse cancers and is implicated in the control of tumor progression. However, the specific contribution from tumor or host CD73 expression to tumor growth remains unknown to date. Here, we show that host CD73 promotes tumor growth in a T cell-dependent manner and that the optimal antitumor effect of CD73 blockade requires inhibiting both tumor and host CD73. Notably, enzymatic activity of CD73 on nonhematopoietic cells limited tumor-infiltrating T cells by controlling antitumor T cell homing to tumors in multiple mouse tumor models. In contrast, CD73 on hematopoietic cells (including CD4⁺CD25⁺ Tregs) inhibited systemic antitumor T cell expansion and effector functions. Thus, CD73 on hematopoietic and nonhematopoietic cells has distinct adenosinergic effects in regulating systemic and local antitumor T cell responses. Importantly, pharmacological blockade of CD73 using its selective inhibitor or an anti-CD73 mAb inhibited tumor growth and completely restored efficacy of adoptive T cell therapy in mice. These findings suggest that both tumor and host CD73 cooperatively protect tumors from incoming antitumor T cells and show the potential of targeting CD73 as a cancer immunotherapy strategy.
Authors:
Long Wang; Jie Fan; Linda F Thompson; Yi Zhang; Tahiro Shin; Tyler J Curiel; Bin Zhang
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2011-05-02
Journal Detail:
Title:  The Journal of clinical investigation     Volume:  121     ISSN:  1558-8238     ISO Abbreviation:  J. Clin. Invest.     Publication Date:  2011 Jun 
Date Detail:
Created Date:  2011-06-02     Completed Date:  2011-08-17     Revised Date:  2014-09-13    
Medline Journal Info:
Nlm Unique ID:  7802877     Medline TA:  J Clin Invest     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2371-82     Citation Subset:  AIM; IM    
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MeSH Terms
Descriptor/Qualifier:
5'-Nucleotidase / antagonists & inhibitors,  deficiency,  immunology,  physiology*
Adenosine / physiology
Adenosine Diphosphate / analogs & derivatives,  pharmacology,  therapeutic use
Animals
Chemotaxis, Leukocyte
Disease Progression
Female
Immunotherapy, Adoptive
Lymphocytes, Tumor-Infiltrating / immunology
Lymphoma, Non-Hodgkin / immunology,  pathology*,  therapy
Melanoma, Experimental / immunology,  pathology*,  therapy
Mice
Mice, Inbred C57BL
Mice, Knockout
Mice, Transgenic
Molecular Targeted Therapy
Ovarian Neoplasms / immunology,  pathology*,  therapy
Peritoneal Neoplasms / immunology,  secondary,  therapy
Radiation Chimera
Second Messenger Systems / physiology
T-Lymphocytes / immunology*
T-Lymphocytes, Regulatory / immunology
Tumor Burden
Grant Support
ID/Acronym/Agency:
2P30 CA054174-17/CA/NCI NIH HHS; AI18220/AI/NIAID NIH HHS; R01 CA149669/CA/NCI NIH HHS; UL1 RR025767/RR/NCRR NIH HHS; UL1 TR000149/TR/NCATS NIH HHS; UL1RR025767/RR/NCRR NIH HHS
Chemical
Reg. No./Substance:
0/alpha,beta-methyleneadenosine 5'-diphosphate; 61D2G4IYVH/Adenosine Diphosphate; EC 3.1.3.5/5'-Nucleotidase; K72T3FS567/Adenosine
Comments/Corrections

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


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