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

doi:10.1080/2162402X.2017.1386826

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-LyMark J. Smyth, Xavier Mariette, Benoît L. Salomon, Guido Kroemer, Sylvie Rusakiewicz, Laurence Zitvogel

Research output: Contribution to journal › Article › peer-review

31 Citations (Scopus)

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.

Original language	English
Article number	e1386826
Journal	OncoImmunology
Volume	7
Issue number	12
DOIs	https://doi.org/10.1080/2162402X.2017.1386826
Publication status	Published - 2 Dec 2018

Keywords

BIRC3
NK cells
TNFα
TRAF1
cancer
immune checkpoint
immunity

Access to Document

10.1080/2162402X.2017.1386826

Cite this

Ivagnès, A., Messaoudene, M., Stoll, G., Routy, B., Fluckiger, A., Yamazaki, T., Iribarren, K., Duong, C. P. M., Fend, L., Caignard, A., Cremer, I., LeCesne, A., Adam, J., Honoré, C., Mir, O., Chaigneau, L., Berger, A., Validire, P., Christidis, C., ... Zitvogel, L. (2018). TNFR2/BIRC3-TRAF1 signaling pathway as a novel NK cell immune checkpoint in cancer. OncoImmunology, 7(12), Article e1386826. https://doi.org/10.1080/2162402X.2017.1386826

@article{6cae5cf8c7ee497eaf4972434203d0a5,

title = "TNFR2/BIRC3-TRAF1 signaling pathway as a novel NK cell immune checkpoint in cancer",

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 = "BIRC3, NK cells, TNFα, TRAF1, cancer, immune checkpoint, immunity",

author = "Alexandre Ivagn{\`e}s and Meriem Messaoudene and Gautier Stoll and Bertrand Routy and Aur{\'e}lie Fluckiger and Takahiro Yamazaki and Kristina Iribarren and Duong, {Connie P.M.} and Laetitia Fend and Anne Caignard and Isabelle Cremer and Axel LeCesne and Julien Adam and Charles Honor{\'e} and Olivier Mir and Lo{\"i}c Chaigneau and Anne Berger and Pierre Validire and Christos Christidis and Brun-Ly, {Val{\'e}rie Le} and Smyth, {Mark J.} and Xavier Mariette and Salomon, {Beno{\^i}t L.} and Guido Kroemer and Sylvie Rusakiewicz and Laurence Zitvogel",

note = "Publisher Copyright: {\textcopyright} 2017, {\textcopyright} 2017 Taylor & Francis Group, LLC.",

year = "2018",

month = dec,

day = "2",

doi = "10.1080/2162402X.2017.1386826",

language = "English",

volume = "7",

journal = "OncoImmunology",

issn = "2162-4011",

number = "12",

}

Ivagnès, A, Messaoudene, M, Stoll, G, Routy, B, Fluckiger, A, Yamazaki, T, Iribarren, K, Duong, CPM, Fend, L, Caignard, A, Cremer, I, LeCesne, A, Adam, J, Honoré, C, Mir, O, Chaigneau, L, Berger, A, Validire, P, Christidis, C, Brun-Ly, VL, Smyth, MJ, Mariette, X, Salomon, BL, Kroemer, G, Rusakiewicz, S & Zitvogel, L 2018, 'TNFR2/BIRC3-TRAF1 signaling pathway as a novel NK cell immune checkpoint in cancer', OncoImmunology, vol. 7, no. 12, e1386826. https://doi.org/10.1080/2162402X.2017.1386826

TY - JOUR

T1 - TNFR2/BIRC3-TRAF1 signaling pathway as a novel NK cell immune checkpoint in cancer

AU - Ivagnès, Alexandre

AU - Messaoudene, Meriem

AU - Stoll, Gautier

AU - Routy, Bertrand

AU - Fluckiger, Aurélie

AU - Yamazaki, Takahiro

AU - Iribarren, Kristina

AU - Duong, Connie P.M.

AU - Fend, Laetitia

AU - Caignard, Anne

AU - Cremer, Isabelle

AU - LeCesne, Axel

AU - Adam, Julien

AU - Honoré, Charles

AU - Mir, Olivier

AU - Chaigneau, Loïc

AU - Berger, Anne

AU - Validire, Pierre

AU - Christidis, Christos

AU - Brun-Ly, Valérie Le

AU - Smyth, Mark J.

AU - Mariette, Xavier

AU - Salomon, Benoît L.

AU - Kroemer, Guido

AU - Rusakiewicz, Sylvie

AU - Zitvogel, Laurence

PY - 2018/12/2

Y1 - 2018/12/2

N2 - 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.

AB - 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.

KW - BIRC3

KW - NK cells

KW - TNFα

KW - TRAF1

KW - cancer

KW - immune checkpoint

KW - immunity

UR - http://www.scopus.com/inward/record.url?scp=85058055864&partnerID=8YFLogxK

U2 - 10.1080/2162402X.2017.1386826

DO - 10.1080/2162402X.2017.1386826

M3 - Article

C2 - 30524877

AN - SCOPUS:85058055864

SN - 2162-4011

VL - 7

JO - OncoImmunology

JF - OncoImmunology

IS - 12

M1 - e1386826

ER -

TNFR2/BIRC3-TRAF1 signaling pathway as a novel NK cell immune checkpoint in cancer

Abstract

Keywords

Access to Document

Other files and links

Cite this