Journal
ONCOIMMUNOLOGY
Volume 5, Issue 12, Pages -Publisher
TAYLOR & FRANCIS INC
DOI: 10.1080/2162402X.2016.1154251
Keywords
immunogenetics; melanoma; NK receptors; natural Killer cells
Categories
Funding
- l'Institut National du Cancer [PLBIO-2011-6]
- PAIR Melanome [2013-0662013]
- l'Association pour la Recherche contre le Cancer (ARC) [3964]
- la Ligue Nationale contre le Cancer (Comite Ile de France)
- l'Assistance Publique des Hopitaux de Paris (APHP) (DRCD, Immumela program)
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Given the NK cell-based immunosurveillance of melanoma, we investigated the prognostic value of NKp46 transcript and NKp30 isoform (NKp30A, NKp30B and NKp30C) profiling in blood of 187 melanoma patients including 13 long survivors (LS), metastatic patients that have controlled the disease. Compared to healthy volunteers (HV), patients had reduced amounts of transcripts of the three NKp30 isoforms (NKp30 A, B and C) but similar ratios between NKp30 isoforms (Delta AB, Delta AC, Delta BC). Stratification of patients according to disease stage showed higher NKp30C and lower NKp46 transcripts in stage IV patients. Furthermore, patients with previous history of conventional chemotherapy displayed reduced NKp30A transcripts. The expression levels of NKp30 isoforms failed to predict survival from sampling of patients, while NKp46 expression predicted melanoma outcome. LS patients displayed elevated NKp30A levels, accordingly high Delta AB and Delta BC ratios, and a unique pattern of rare allelic variants of NKp30 SNPs. Moreover, NK cells from LS displayed correlated NKp30/NKp46 membrane expression, high spontaneous and NKp30- or NKp46-triggered degranulation. These data outline the impact of NKp30 and NKp46 transcripts on melanoma evolution and identify unique genetic features of NKp30 associated with higher NK activation in rare LS melanoma patients that control a metastatic disease.
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