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Production by Invariant NK T Cells in Advanced Cancer1
*
Cancer Biology Program, Hematology/Oncology Division, Department of Medicine, Beth Israel-Deaconess Medical Center and Harvard Medical School, Boston, MA 02215;
Pharmaceutical Research Laboratory, Kirin Brewery, Gunma, Japan; and
Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Boston, MA 02115
Invariant NK T cells express certain NK cell receptors and an
invariant TCR
chain specific for the MHC class I-like CD1d protein.
These invariant NK T cells can regulate diverse immune responses in
mice, including antitumor responses, through mechanisms including rapid
production of IL-4 and IFN-
, but their physiological functions
remain uncertain. Invariant NK T cells were markedly decreased in
peripheral blood from advanced prostate cancer patients, and their ex
vivo expansion with a CD1d-presented lipid Ag (-galactosylceramide)
was diminished compared with healthy donors. Invariant NK T cells from
healthy donors produced high levels of both IFN- and IL-4. In
contrast, whereas invariant NK T cells from prostate cancer patients
also produced IL-4, they had diminished IFN- production and a
striking decrease in their IFN-:IL-4 ratio. The IFN- deficit was
specific to the invariant NK T cells, as bulk T cells from prostate
cancer patients produced normal levels of IFN- and IL-4. These
findings support an immunoregulatory function for invariant NK T cells
in humans mediated by differential production of Th1 vs Th2 cytokines.
They further indicate that antitumor responses may be suppressed by the
marked Th2 bias of invariant NK T cells in advanced cancer
patients.
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