Enrichment of human CD4+ V(alpha)24/Vbeta11 invariant NKT cells in intrahepatic malignant tumors.

Details

Serval ID
serval:BIB_E89A801F10DC
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Enrichment of human CD4+ V(alpha)24/Vbeta11 invariant NKT cells in intrahepatic malignant tumors.
Journal
Journal of Immunology
Author(s)
Bricard G., Cesson V., Devevre E., Bouzourene H., Barbey C., Rufer N., Im J.S., Alves P.M., Martinet O., Halkic N., Cerottini J.C., Romero P., Porcelli S.A., Macdonald H.R., Speiser D.E.
ISSN
1550-6606[electronic]
Publication state
Published
Issued date
2009
Volume
182
Number
8
Pages
5140-5151
Language
english
Abstract
Invariant NKT cells (iNKT cells) recognize glycolipid Ags via an invariant TCR alpha-chain and play a central role in various immune responses. Although human CD4(+) and CD4(-) iNKT cell subsets both produce Th1 cytokines, the CD4(+) subset displays an enhanced ability to secrete Th2 cytokines and shows regulatory activity. We performed an ex vivo analysis of blood, liver, and tumor iNKT cells from patients with hepatocellular carcinoma and metastases from uveal melanoma or colon carcinoma. Frequencies of Valpha24/Vbeta11 iNKT cells were increased in tumors, especially in patients with hepatocellular carcinoma. The proportions of CD4(+), double negative, and CD8alpha(+) iNKT cell subsets in the blood of patients were similar to those of healthy donors. However, we consistently found that the proportion of CD4(+) iNKT cells increased gradually from blood to liver to tumor. Furthermore, CD4(+) iNKT cell clones generated from healthy donors were functionally distinct from their CD4(-) counterparts, exhibiting higher Th2 cytokine production and lower cytolytic activity. Thus, in the tumor microenvironment the iNKT cell repertoire is modified by the enrichment of CD4(+) iNKT cells, a subset able to generate Th2 cytokines that can inhibit the expansion of tumor Ag-specific CD8(+) T cells. Because CD4(+) iNKT cells appear inefficient in tumor defense and may even favor tumor growth and recurrence, novel iNKT-targeted therapies should restore CD4(-) iNKT cells at the tumor site and specifically induce Th1 cytokine production from all iNKT cell subsets.
Keywords
Adult, Aged, Aged, 80 and over, Antigens, CD1d, Antigens, CD3, CD4-Positive T-Lymphocytes, Cloning, Molecular, Female, Health, Hela Cells, Humans, Liver Neoplasms, Male, Middle Aged, Natural Killer T-Cells, Receptors, Antigen, T-Cell
Pubmed
Web of science
Open Access
Yes
Create date
18/05/2009 18:35
Last modification date
20/08/2019 17:11
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