Expression pattern of HLA class I antigens in renal cell carcinoma and primary cell line cultures: methodological implications for immunotherapy.

Background: Renal cell carcinomas have developed various strategies to escape immune cell recognition, including down-regulation or loss of classic HLA class I antigens (A, B, C) and aberrant expression of non-classic HLA class I antigens (G, E). In this study both classic and non-classic HLA class I antigens were tested in tumor specimens and established primary cell cultures derived from renal cell carcinoma patients.

Material/methods: HLA class I antigens were evaluated by immunohistochemical staining and the intensity of cytoplasmic staining was measured semiquantitatively.

Reduced inducibility of SOCS3 by interferon gamma associates with higher resistance of human breast cancer lines as compared to normal mammary epithelial cells.

The resistance to interferons (IFNs) limits their anticancer therapeutic efficacy. Here we studied the antiproliferative effect of interferon gamma in relation to SOCS3 expression in a panel of breast cancer cell lines and normal mammary epithelial cells. Compared to normal cells most breast cancer lines (7/8) were highly resistant to IFN-gamma.

Interferon-alpha treatment may negatively influence disease progression in melanoma patients by hyperactivation of STAT3 protein.

Interferon-alpha (IFN-alpha) is an important drug used in anti-melanoma therapy. However, metastases eventually reappear in almost 60% of melanoma patients, who have received adjuvant cytokine therapy suggesting that IFN-alpha can paradoxically promote disease progression in some cases, at least. In this study, we have investigated the possibility that a growth-promoting STAT3 protein might be activated by interferon-alpha in melanoma cells.

Defective IFNα/γ-induced STAT3 protein activation in human malignant melanoma cells.

Signal transducer and activator of transcription 3 (STAT3) protein has been documented as a significant mediator of interferon (IFN) signaling. Physiological STAT3 phosphorylation involves tyrosine (Y705) and serine (S727) activation. Impairment of STAT3 protein levels and/or of STAT3 phosphorylation after IFN treatment has been found in many pathological conditions such as cancer, immunopathy and inflammatory disease.

Development of IFN-gamma resistance is associated with attenuation of SOCS genes induction and constitutive expression of SOCS 3 in melanoma cells.

The resistance to interferons (IFNs) limits their anticancer therapeutic efficacy. Here we studied the evolution of an IFN-resistant state in vitro using melanoma cell lines. We found that the cells became less sensitive to antiproliferative effect of IFN-gamma after prolonged cultivation enabling us to isolate sensitive and resistant subclones of the parental line.