Nitrite Destruction as a Presumptive Test for the Determination of Water Pollution

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Acquired IFNγ 3 resistance impairs anti-Tumor immunity and gives rise to T-cell-resistant melanoma lesions

Melanoma treatment has been revolutionized by antibody-based immunotherapies. IFN 3 secretion by CD8 + T cells is critical for therapy efficacy having anti-proliferative and pro-Apoptotic effects on tumour cells. Our study demonstrates a genetic evolution of IFN 3 resistance in different melanoma patient models. Chromosomal alterations and subsequent inactivating mutations in genes of the IFN 3 signalling cascade, most often JAK1 or JAK2, protect melanoma cells from anti-Tumour IFN 3 activity. JAK1/2 mutants further evolve into T-cell-resistant HLA class I-negative lesions with genes involved in antigen presentation silenced and no longer inducible by IFN 3. Allelic JAK1/2 losses predisposing to IFN 3 resistance development are frequent in melanoma. Subclones harbouring inactivating mutations emerge under various immunotherapies but are also detectable in pre-Treatment biopsies. Our data demonstrate that JAK1/2 deficiency protects melanoma from anti-Tumour IFN 3 activity and results in T-cell-resistant HLA class I-negative lesions. Screening for mechanisms of IFN 3 resistance should be considered in therapeutic decision-making. © 2017 The Author(s)