| Literature DB >> 30524877 |
Alexandre Ivagnès1,2,3, Meriem Messaoudene1,2, Gautier Stoll4,5,6,7, Bertrand Routy1,2,3, Aurélie Fluckiger1,2, Takahiro Yamazaki8, Kristina Iribarren4,5,6, Connie P M Duong1,2, Laetitia Fend9, Anne Caignard10,11, Isabelle Cremer4,6,7, Axel LeCesne1,12, Julien Adam1,13,14, Charles Honoré1,15, Olivier Mir1,12, Loïc Chaigneau16, Anne Berger6,17, Pierre Validire18,19, Christos Christidis6,19,20, Valérie Le Brun-Ly21, Mark J Smyth22, Xavier Mariette3,23, Benoît L Salomon24, Guido Kroemer4,5,6,7,24,25,26,27, Sylvie Rusakiewicz28, Laurence Zitvogel1,2,3,29.
Abstract
Natural Killer (NK) cells control metastatic dissemination of murine tumors and are an important prognostic factor in several human malignancies. However, tumor cells hijack many of the NK cell functional features compromising their tumoricidal activity. Here, we show a deleterious role of the TNFα/TNFR2/BIRC3/TRAF1 signaling cascade in NK cells from the tumor microenvironment (TME). TNFα induces BIRC3/cIAP2 transcripts and reduces NKp46/NCR1 transcription and surface expression on NK cells, promoting metastases dissemination in mice and poor prognosis in GIST patients. NKp30 engagement, by promoting the release of TNFα, also contributes to BIRC3 upregulation, and more so in patients expressing predominantly NKp30C isoforms. These findings reveal that in the absence of IL-12 or a Th1-geared TME, TNFα can be considered as a negative regulatory cytokine for innate effectors.Entities:
Keywords: BIRC3; NK cells; TNFα; TRAF1; cancer; immune checkpoint; immunity
Year: 2017 PMID： 30524877 PMCID： PMC6279330 DOI： 10.1080/2162402X.2017.1386826
Source DB: PubMed Journal: Oncoimmunology ISSN： 2162-4011 Impact factor: 8.110