Journal article
Targeting cytokine signaling checkpoint CIS activates NK cells to protect from tumor initiation and metastasis
EM Putz, C Guillerey, K Kos, K Stannard, K Miles, RB Delconte, K Takeda, SE Nicholson, ND Huntington, MJ Smyth
Oncoimmunology | TAYLOR & FRANCIS INC | Published : 2017
Abstract
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 checkp..
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Awarded by Harry J. Lloyd Charitable Trust
Funding Acknowledgements
This work was supported in part by the National Health and Medical Research Council (NHMRC) project grants 1049407, 1066770 and 1057852 and program grant 1016647. E.M. Putz was supported by an Erwin Schroedinger Fellowship of the Austrian Science Fund (J-3635). N. D. Huntington by a Melanoma Research Grant from the Harry J Lloyd Charitable Trust and R.B. Delconte by a Leukaemia Foundation scholarship. C. Guillerey and M.J. Smyth were supported by NHMRC Early Career (1107417) and Senior Principal Research Fellowships (1078671), respectively. This work was also supported in part by an NHMRC Independent Research Institute Infrastructure Support scheme grant and a Victorian State Government Operational Infrastructure Scheme grant.