Modulation of the tumor cell phenotype by IFN-γ results in resistance of uveal melanoma cells to granule-mediated lysis by cytotoxic lymphocytes

Kristian Hallermalm, Kazutake Seki, Anna De Geer, Bruce Motyka, R. Chris Bleackley, Martine J. Jager, Christopher J. Froelich, Rolf Kiessling, Victor Levitsky, Jelena Levitskaya

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)3766-3774
Number of pages9
JournalJournal of Immunology
Volume180
Issue number6
StatePublished - Mar 15 2008

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Lymphocytes
Phenotype
Neoplasms
Granzymes
Perforin
Epigenomics
Uveal melanoma
Neoplasm Metastasis
Serum
Therapeutics

ASJC Scopus subject areas

  • Immunology

Cite this

Hallermalm, K., Seki, K., De Geer, A., Motyka, B., Bleackley, R. C., Jager, M. J., ... Levitskaya, J. (2008). Modulation of the tumor cell phenotype by IFN-γ results in resistance of uveal melanoma cells to granule-mediated lysis by cytotoxic lymphocytes. Journal of Immunology, 180(6), 3766-3774.

Modulation of the tumor cell phenotype by IFN-γ results in resistance of uveal melanoma cells to granule-mediated lysis by cytotoxic lymphocytes. / Hallermalm, Kristian; Seki, Kazutake; De Geer, Anna; Motyka, Bruce; Bleackley, R. Chris; Jager, Martine J.; Froelich, Christopher J.; Kiessling, Rolf; Levitsky, Victor; Levitskaya, Jelena.

In: Journal of Immunology, Vol. 180, No. 6, 15.03.2008, p. 3766-3774.

Research output: Contribution to journalArticle

Hallermalm, K, Seki, K, De Geer, A, Motyka, B, Bleackley, RC, Jager, MJ, Froelich, CJ, Kiessling, R, Levitsky, V & Levitskaya, J 2008, 'Modulation of the tumor cell phenotype by IFN-γ results in resistance of uveal melanoma cells to granule-mediated lysis by cytotoxic lymphocytes', Journal of Immunology, vol. 180, no. 6, pp. 3766-3774.
Hallermalm, Kristian ; Seki, Kazutake ; De Geer, Anna ; Motyka, Bruce ; Bleackley, R. Chris ; Jager, Martine J. ; Froelich, Christopher J. ; Kiessling, Rolf ; Levitsky, Victor ; Levitskaya, Jelena. / Modulation of the tumor cell phenotype by IFN-γ results in resistance of uveal melanoma cells to granule-mediated lysis by cytotoxic lymphocytes. In: Journal of Immunology. 2008 ; Vol. 180, No. 6. pp. 3766-3774.
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