Melanoma NOS1 expression promotes dysfunctional IFN signaling.

Liu, Qiuzhen and Tomei, Sara and Ascierto, Maria Libera and De Giorgi, Valeria and Bedognetti, Davide and Dai, Cuilian and Uccellini, Lorenzo and Spivey, Tara and Pos, Zoltan and Thomas, Jaime and Reinboth, Jennifer and Murtas, Daniela and Zhang, Qianbing and Chouchane, Lotfi and Weiss, Geoffrey R. and Slingluff, Craig L. and Lee, Peter P. and Rosenberg, Steven A. and Alter, Harvey and Yao, Kaitai and Wang, Ena and Marincola, Francesco M. (2014) Melanoma NOS1 expression promotes dysfunctional IFN signaling. The Journal of clinical investigation, 124 (5). pp. 2147-59. ISSN 1558-8238

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In multiple forms of cancer, constitutive activation of type I IFN signaling is a critical consequence of immune surveillance against cancer; however, PBMCs isolated from cancer patients exhibit depressed STAT1 phosphorylation in response to IFN-α, suggesting IFN signaling dysfunction. Here, we demonstrated in a coculture system that melanoma cells differentially impairs the IFN-α response in PBMCs and that the inhibitory potential of a particular melanoma cell correlates with NOS1 expression. Comparison of gene transcription and array comparative genomic hybridization (aCGH) between melanoma cells from different patients indicated that suppression of IFN-α signaling correlates with an amplification of the NOS1 locus within segment 12q22-24. Evaluation of NOS1 levels in melanomas and IFN responsiveness of purified PBMCs from patients indicated a negative correlation between NOS1 expression in melanomas and the responsiveness of PBMCs to IFN-α. Furthermore, in an explorative study, NOS1 expression in melanoma metastases was negatively associated with patient response to adoptive T cell therapy. This study provides a link between cancer cell phenotype and IFN signal dysfunction in circulating immune cells.

Item Type: Article
Subjects: Q Science / természettudomány > Q1 Science (General) / természettudomány általában
R Medicine / orvostudomány > R1 Medicine (General) / orvostudomány általában
Depositing User: Zoltán Pós
Date Deposited: 07 Feb 2015 12:22
Last Modified: 10 Dec 2015 22:52

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