Transcriptional Reprogramming and Constitutive PD-L1 Expression in Melanoma Are Associated with Dedifferentiation and Activation of Interferon and Tumour Necrosis Factor Signalling Pathways
نویسندگان
چکیده
Melanoma is the most aggressive type of skin cancer, with increasing incidence worldwide. Advances in targeted therapy and immunotherapy have improved survival melanoma patients experiencing recurrent disease, but unfortunately treatment resistance frequently reduces patient survival. Resistance to associated transcriptomic changes has also been shown be accompanied by increased expression programmed death ligand 1 (PD-L1), a potent inhibitor immune response. Intrinsic upregulation PD-L1 genome-wide DNA hypomethylation widespread alterations gene cell lines. However, an in-depth analysis landscape cells intrinsically upregulated lacking. To determine melanoma, we investigated transcriptomes melanomas constitutive versus inducible (referred as PD-L1CON PD-L1IND). RNA-Seq was performed on seven lines ten low PD-L1IND expression. We observed that had reprogrammed transcriptome characteristic pattern dedifferentiated expression, together active interferon (IFN) tumour necrosis factor (TNF) signalling pathways. Furthermore, identified key transcription factors were differentially expressed Overall, our studies describe reprogramming
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متن کامل
Interferon Receptor Signaling Pathways Regulating PD-L1 and PD-L2 Expression.
PD-L1 and PD-L2 are ligands for the PD-1 immune inhibiting checkpoint that can be induced in tumors by interferon exposure, leading to immune evasion. This process is important for immunotherapy based on PD-1 blockade. We examined the specific molecules involved in interferon-induced signaling that regulates PD-L1 and PD-L2 expression in melanoma cells. These studies revealed that the interfero...
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ژورنال
عنوان ژورنال: Cancers
سال: 2021
ISSN: ['2072-6694']
DOI: https://doi.org/10.3390/cancers13174250