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Circulating myeloid dendritic cells of advanced cancer patients result in reduced activation and a biased cytokine profile in invariant NKT cells.
- Source :
-
Journal of immunology (Baltimore, Md. : 1950) [J Immunol] 2008 Jun 01; Vol. 180 (11), pp. 7287-93. - Publication Year :
- 2008
-
Abstract
- CD1d-restricted invariant NKT (iNKT) cells play important regulatory roles in various immune responses, including antitumor immune responses. Previous studies have demonstrated quantitative and qualitative defects in iNKT cells of cancer patients, and these defects are clinically relevant as they are associated with poor prognosis. In this study we demonstrate that defects in the iNKT cell population can, at least in part, be attributed to defective interactions between iNKT cells and CD1d-expressing circulating myeloid dendritic cells (mDC), as mDC of patients with advanced melanoma and renal cell cancer reduced the activation and Th1 cytokine production of healthy donor-derived iNKT cells. Interestingly, this reduced activation of iNKT cells was restricted to patients with low circulating iNKT cell numbers and could be reversed by IL-12 and in part by the neutralization of TGF-beta, but it was further reduced by the neutralization of IL-10 in vitro. Additional experiments revealed discordant roles for TGF-beta and IL-10 on human iNKT cells, because TGF-beta suppressed iNKT cell activation and proliferation and IFN-gamma production while IL-10 was identified as a cytokine involved in stimulating the activation and expansion of iNKT cells that could subsequently suppress NK cell and T cell responses.
- Subjects :
- Adult
Aged
Antigens, CD1 immunology
Cell Line
Cytokines immunology
Dendritic Cells metabolism
Female
Humans
Interferon-gamma immunology
Interferon-gamma metabolism
Interleukin-10 immunology
Killer Cells, Natural metabolism
Lymphocyte Activation
Male
Middle Aged
Myeloid Cells immunology
Myeloid Cells metabolism
Neoplasms metabolism
T-Lymphocyte Subsets metabolism
Transforming Growth Factor beta immunology
Antigens, CD1 metabolism
Cytokines metabolism
Dendritic Cells immunology
Killer Cells, Natural immunology
Neoplasms immunology
T-Lymphocyte Subsets immunology
Subjects
Details
- Language :
- English
- ISSN :
- 0022-1767
- Volume :
- 180
- Issue :
- 11
- Database :
- MEDLINE
- Journal :
- Journal of immunology (Baltimore, Md. : 1950)
- Publication Type :
- Academic Journal
- Accession number :
- 18490728
- Full Text :
- https://doi.org/10.4049/jimmunol.180.11.7287