Targeting cytokine signaling checkpoint CIS activates NK cells to protect from tumor initiation and metastasis

The cytokine-induced SH2-containing protein CIS belongs to the suppressor of cytokine signaling (SOCS) protein family. Here, we show the critical role of CIS in suppressing natural killer (NK) cell control of tumor initiation and metastasis. Cish-deficient mice were highly resistant to methylcholant...

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Veröffentlicht in:Oncoimmunology Jg. 6; H. 2; S. e1267892
Hauptverfasser: Putz, Eva M., Guillerey, Camille, Kos, Kevin, Stannard, Kimberley, Miles, Kim, Delconte, Rebecca B., Takeda, Kazuyoshi, Nicholson, Sandra E., Huntington, Nicholas D., Smyth, Mark J.
Format: Journal Article
Sprache:Englisch
Veröffentlicht: United States Taylor & Francis 01.02.2017
Taylor & Francis Group
Schlagworte:
Cancer
cytokine signaling
immunotherapy
metastasis
NK cells
Original Research
cytokine signaling
NK cells
metastasis
immunotherapy
Cancer
ISSN:2162-402X, 2162-4011, 2162-402X
Online-Zugang:Volltext
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Zusammenfassung:The cytokine-induced SH2-containing protein CIS belongs to the suppressor of cytokine signaling (SOCS) protein family. Here, we show the critical role of CIS in suppressing natural killer (NK) cell control of tumor initiation and metastasis. Cish-deficient mice were highly resistant to methylcholanthrene-induced sarcoma formation and protected from lung metastasis of B16F10 melanoma and RM-1 prostate carcinoma cells. In contrast, the growth of primary subcutaneous tumors, including those expressing the foreign antigen OVA, was unchanged in Cish-deficient mice. The combination of Cish deficiency and relevant targeted and immuno-therapies such as combined BRAF and MEK inhibitors, immune checkpoint blockade antibodies, IL-2 and type I interferon revealed further improved control of metastasis. The data clearly indicate that targeting CIS promotes NK cell antitumor functions and CIS holds great promise as a novel target in NK cell immunotherapy.
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Supplemental data for this article can be accessed on the publisher's website.
ISSN:2162-402X
2162-4011
2162-402X
DOI:10.1080/2162402X.2016.1267892