Tumor
cells treated with IL-10 were shown to have
decreased but peptide inducible expression
of MHC class I, decreased sensitivity to
MHC class I restricted CTL and increased
NK sensitivity. These findings could be
explained, at least partially, by a down-regulation
of TAP1/TAP2 expression. Here IT9302, a
nanomeric peptide (AYMTMKIRN), homologous
to the C-terminal of the human IL-10 sequence,
was demonstrated to mimic these previously
described IL-10 effects on MHC class I related
molecules and functions. We observed a dose
dependent down-regulation of MHC class I
at the cell surface of melanoma cells after
24 hours treatment with IT9302. The IL-10
homologue peptide also caused a dose dependent
inhibition of the IFN-? mediated surface
induction of MHC class I in a melanoma cell
line. |
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We
demonstrated, using Western blot and flow
cytometry, that IT9302 inhibits the expression
of TAP1 and TAP2 proteins but not MHC class
I heavy chain or LMP2 molecules.
Finally, peptide-treated melanoma cells
were shown to be more sensitive to lysis
by NK cells in a dose dependent way. Taken
together, these results demonstrate that
a small synthetic peptide derived from IL-10
can mimic the antigen presentation related
effects mediated by this cytokine in human
melanomas and increase tumor sensitivity
to NK cells, which can be relevant in the
designing of future strategies for cancer
immune therapy.
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