Interferon‐γ‐Induced MHC Class I Expression and Defects in Jak/Stat Signalling in Methylcholanthrene‐Induced Sarcomas

Abstract

There was a tendency towards a higher MHC expression after IFN-g stimulation in tumour lines from immunocompetent mice compared to immunodeficient mice, but no common maximum MHC class I expression level was found for the 78 tumour cell lines. Three of the tumour lines, all from immunodeficient mice, completely failed to respond to IFN-g by up-regulating MHC class I expression. The same three also displayed absence of IFN-g-induced Stat1b tyrosine phosphorylation and low Stat1a tyrosine phosphorylation, indicating a defect in the signal transduction pathway affecting phosphorylation of Stat1. These findings strongly suggest a link between defects in Stat1 phosphorylation and the failure to up-regulate MHC class I. In all tumour lines tested, the Stat1 Western blotting revealed a 78 kDa protein (p78) not previously described.

Radiation-Induced IFN-γ Production within the Tumor Microenvironment Influences Antitumor Immunity

“…In addition to its role as a proinflammatory cytokine, IFN-␥ is capable of inducing MHC class I expression on a variety of cell types, including most tumor cells (28). The result of MHC upregulation on the surface of the tumor cells is recognition by CTL.…”

“…STAT1 is a key transcription factor in IFN-␥ signaling processes and is known to regulate expression of class I and caspases in responsive cells (27,28). Because STAT1 controls the processes within cells that render them susceptible to CTL recognition and lysis, we asked whether differences in active STAT1 could account for the variation in class I expression and lytic susceptibility in the tumor cells following localized radiation.…”

The Direct Effect of IL-12 on Tumor Cells: IL-12 Acts Directly on Tumor Cells to Activate NF-κB and Enhance IFN-γ-Mediated STAT1 Phosphorylation

“…It was also reported that the sensitivity to IFN-␥ of tumor cells affects tumorigenicity, response to IL-12 therapy and anti-angiogenesis in mice (11). STAT1 is a regulator of gene transcription in the IFNs signaling pathway (12)(13)(14), and mutation of STAT1 can induce IFN-␥ insensitivity in tumor cells (15). The STAT1-dependent signaling is also important for expression of MHC class I in some cell types (16,17).…”

Evolutional change of karyotype with t(8;9)(p22;p24) and HLA-DR immunophenotype in relapsed acute myeloid leukemia

“…2 Cytogenetic analysis of bone marrow aspirate at relapse 7 months after initial diagnosis showed translocation between short arm of chromosome 8 and 9 t(8;9)(p22; p24), as indicated by white arrowhead leukemogenesis. Data from in vitro studies showed a link between JAK2/Stat1 signaling pathway activation and MHC expression [22][23][24]. IFN-c induces tyrosine phosphorylation of the tyrosine kinases Jak1, Jak2 and of Stat1 alpha.…”