TY - JOUR
T1 - Modulation of the tumor cell phenotype by IFN-γ results in resistance of uveal melanoma cells to granule-mediated lysis by cytotoxic lymphocytes
AU - Hallermalm, Kristian
AU - Seki, Kazutake
AU - De Geer, Anna
AU - Motyka, Bruce
AU - Bleackley, R. Chris
AU - Jager, Martine J.
AU - Froelich, Christopher J.
AU - Kiessling, Rolf
AU - Levitsky, Victor
AU - Levitskaya, Jelena
PY - 2008/3/15
Y1 - 2008/3/15
N2 - IFN-γ, a pleiotropic immune regulator, is implicated in both tumor immune surveillance and selection of tumor variants resistant to immune control, i.e., immunoediting. In uveal melanoma patients, elevated serum levels of IFN-γ correlate with the spread of metastasis and represent a negative prognostic marker. Treatment with IFN-γ boosted the MHC class I presentation machinery in uveal melanoma cells but suppressed their MHC class I-restricted CTL lysis. Tumor cells exposed to IFN-γ efficiently activated specific CTL but were less susceptible to permeabilization by perforin and exhibited a decreased capacity to bind and incorporate granzyme B. These results define a novel mechanism of resistance to granule-mediated CTL lysis in human tumors. Furthermore, the data suggest that immunoediting is not limited to genetic or epigenetic changes resulting in stable cellular phenotypes but also involves an inducible modulation of tumor cells in response to a microenvironment associated with immune activation.
AB - IFN-γ, a pleiotropic immune regulator, is implicated in both tumor immune surveillance and selection of tumor variants resistant to immune control, i.e., immunoediting. In uveal melanoma patients, elevated serum levels of IFN-γ correlate with the spread of metastasis and represent a negative prognostic marker. Treatment with IFN-γ boosted the MHC class I presentation machinery in uveal melanoma cells but suppressed their MHC class I-restricted CTL lysis. Tumor cells exposed to IFN-γ efficiently activated specific CTL but were less susceptible to permeabilization by perforin and exhibited a decreased capacity to bind and incorporate granzyme B. These results define a novel mechanism of resistance to granule-mediated CTL lysis in human tumors. Furthermore, the data suggest that immunoediting is not limited to genetic or epigenetic changes resulting in stable cellular phenotypes but also involves an inducible modulation of tumor cells in response to a microenvironment associated with immune activation.
UR - http://www.scopus.com/inward/record.url?scp=44849098983&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=44849098983&partnerID=8YFLogxK
M3 - Article
C2 - 18322182
AN - SCOPUS:44849098983
SN - 0022-1767
VL - 180
SP - 3766
EP - 3774
JO - Journal of Immunology
JF - Journal of Immunology
IS - 6
ER -