OncoImmunology (Dec 2018)
TNFR2/BIRC3-TRAF1 signaling pathway as a novel NK cell immune checkpoint in cancer
- Alexandre Ivagnès,
- Meriem Messaoudene,
- Gautier Stoll,
- Bertrand Routy,
- Aurélie Fluckiger,
- Takahiro Yamazaki,
- Kristina Iribarren,
- Connie P. M. Duong,
- Laetitia Fend,
- Anne Caignard,
- Isabelle Cremer,
- Axel LeCesne,
- Julien Adam,
- Charles Honoré,
- Olivier Mir,
- Loïc Chaigneau,
- Anne Berger,
- Pierre Validire,
- Christos Christidis,
- Valérie Le Brun-Ly,
- Mark J. Smyth,
- Xavier Mariette,
- Benoît L. Salomon,
- Guido Kroemer,
- Sylvie Rusakiewicz,
- Laurence Zitvogel
Affiliations
- Alexandre Ivagnès
- Institut de Cancérologie Gustave Roussy Cancer Campus (GRCC)
- Meriem Messaoudene
- Institut de Cancérologie Gustave Roussy Cancer Campus (GRCC)
- Gautier Stoll
- INSERM, U1138, Centre de Recherche des Cordeliers
- Bertrand Routy
- Institut de Cancérologie Gustave Roussy Cancer Campus (GRCC)
- Aurélie Fluckiger
- Institut de Cancérologie Gustave Roussy Cancer Campus (GRCC)
- Takahiro Yamazaki
- Weill Cornell Medical College
- Kristina Iribarren
- INSERM, U1138, Centre de Recherche des Cordeliers
- Connie P. M. Duong
- Institut de Cancérologie Gustave Roussy Cancer Campus (GRCC)
- Laetitia Fend
- Transgene S.A.
- Anne Caignard
- INSERM, U1160, Université Paris Diderot, Sorbonne Paris Cité
- Isabelle Cremer
- INSERM, U1138, Centre de Recherche des Cordeliers
- Axel LeCesne
- Institut de Cancérologie Gustave Roussy Cancer Campus (GRCC)
- Julien Adam
- Institut de Cancérologie Gustave Roussy Cancer Campus (GRCC)
- Charles Honoré
- Institut de Cancérologie Gustave Roussy Cancer Campus (GRCC)
- Olivier Mir
- Institut de Cancérologie Gustave Roussy Cancer Campus (GRCC)
- Loïc Chaigneau
- Centre Hospitalier Universitaire Jean Minjoz
- Anne Berger
- Université Paris Descartes/Paris V, Sorbonne Paris Cité, 15 rue de l'Ecole de Médecine
- Pierre Validire
- Institut Mutualiste Montsouris
- Christos Christidis
- Université Paris Descartes/Paris V, Sorbonne Paris Cité, 15 rue de l'Ecole de Médecine
- Valérie Le Brun-Ly
- Centre hospitalier régional universitaire de Limoges Dupuytren
- Mark J. Smyth
- Immunology in Cancer and Infection Laboratory, QIMR Berghofer Medical Research Institute
- Xavier Mariette
- Université Paris Sud, Université Paris-Saclay, Faculté de Médecine
- Benoît L. Salomon
- Sorbonne Universités, UPMC Univ Paris 06, INSERM, CNRS, Centre d'Immunologie et des Maladies Infectieuses (CIMI-Paris)
- Guido Kroemer
- INSERM, U1138, Centre de Recherche des Cordeliers
- Sylvie Rusakiewicz
- Center of Experimental Therapeutics, Ludwig Center for Cancer Res
- Laurence Zitvogel
- Institut de Cancérologie Gustave Roussy Cancer Campus (GRCC)
- DOI
- https://doi.org/10.1080/2162402X.2017.1386826
- Journal volume & issue
-
Vol. 7,
no. 12
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.
Keywords
