Unknown

Dataset Information

0

Melanoma NOS1 expression promotes dysfunctional IFN signaling.


ABSTRACT: 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-?, suggesting IFN signaling dysfunction. Here, we demonstrated in a coculture system that melanoma cells differentially impairs the IFN-? 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-? 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-?. 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.

SUBMITTER: Liu Q 

PROVIDER: S-EPMC4001531 | biostudies-literature | 2014 May

REPOSITORIES: biostudies-literature

altmetric image

Publications


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. C  ...[more]

Similar Datasets

| S-EPMC7068236 | biostudies-literature
| S-EPMC2671382 | biostudies-literature
| S-EPMC4577833 | biostudies-literature
| S-EPMC6737652 | biostudies-literature
| S-EPMC6389959 | biostudies-literature
2021-12-31 | GSE166287 | GEO
| S-EPMC4148478 | biostudies-literature
2013-12-31 | E-GEOD-44848 | biostudies-arrayexpress
| S-EPMC10524955 | biostudies-literature
| S-EPMC5192500 | biostudies-literature