Transcriptional Response of T Cells to IFN-α: Changes Induced in IFN-α-Sensitive and Resistant Cutaneous T Cell Lymphoma

Interferon-α (IFN-α) therapy is commonly used in the treatment of neoplastic and autoimmune diseases, including cutaneous T cell lymphoma (CTCL). However, the IFN-α response is unpredictable, and the IFN-α cell targets and pathways are only partially understood. To delineate the molecular mechanisms of IFN-α activity, gene expression profiling was performed in a time-course experiment of both IFN-α sensitive and IFN-α-resistant variants of a CTCL cell line. These experiments revealed that IFN-α is responsible for the regulation of hundreds of genes in both variants and predominantly involves genes implicated in signal transduction, cell cycle control, apoptosis, and transcription regulation. Specifically, the IFN-α response of tumoral T cells is due to a combination of induction of apoptosis in which TNFSF10 and HSXIAPAF1 may play an important role and cell cycle arrest achieved by downregulation of CDK4 and CCNG2 and upregulation of CDKN2C and tumor suppressor genes (TSGs). Resistance to IFN-α appears to...