Linked Life Data

15313928

Source:http://linkedlifedata.com/resource/pubmed/id/15313928

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
16
pubmed:dateCreated
2004-8-17
pubmed:abstractText
T cells infiltrating tumors have a decreased expression of signal transduction proteins, a diminished ability to proliferate, and a decreased production of cytokines. The mechanisms causing these changes have remained unclear. We demonstrated recently that peritoneal macrophages stimulated with interleukin 4 + interleukin 13 produce arginase I, which decreases the expression of the T-cell receptor CD3zeta chain and impairs T-cell responses. Using a 3LL murine lung carcinoma model we tested whether arginase I was produced in the tumor microenvironment and could decrease CD3zeta expression and impair T-cell function. The results show that a subpopulation of mature tumor-associated myeloid cells express high levels of arginase I, whereas tumor cells and infiltrating lymphocytes do not. Arginase I expression in the tumor was seen on day 7 after tumor injection. Tumor-associated myeloid cells also expressed high levels of cationic amino acid transporter 2B, which allowed them to rapidly incorporate L-Arginine (L-Arg) and deplete extracellular L-Arg in vitro. L-Arg depletion by tumor-associated myeloid cells blocked the re-expression of CD3zeta in stimulated T cells and inhibited antigen-specific proliferation of OT-1 and OT-2 cells. The injection of the arginase inhibitor N-hydroxy-nor-L-Arg blocked growth of s.c. 3LL lung carcinoma in mice. High levels of arginase I were also found in tumor samples of patients with non-small cell carcinoma. Therefore, arginase I production by mature myeloid cells in the tumor microenvironment may be a central mechanism for tumor evasion and may represent a target for new therapies.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
0008-5472
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
64
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
5839-49
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
2004
pubmed:articleTitle
Arginase I production in the tumor microenvironment by mature myeloid cells inhibits T-cell receptor expression and antigen-specific T-cell responses.
pubmed:affiliation
Tumor Immunology Program, Stanley S. Scott Cancer Center, Louisiana State University, Health Sciences Center, New Orleans, Louisiana 70112, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.