Nilotinib combined with interleukin-2 mediates antitumor and immunological effects in a B16 melanoma model

Geisler,K.; Reischer,A.; Kroeger,I.; Jacobs,B.; Meinhardt,K.; Bauer,R.; Ryffel,B.; Mackensen,A.; Ullrich,E.

doi:10.3892/or.2014.3070

May-2014 Volume 31 Issue 5

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May-2014 Volume 31 Issue 5

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Article

Nilotinib combined with interleukin-2 mediates antitumor and immunological effects in a B16 melanoma model

Authors:
- K. Geisler
- A. Reischer
- I. Kroeger
- B. Jacobs
- K. Meinhardt
- R. Bauer
- B. Ryffel
- A. Mackensen
- E. Ullrich
View Affiliations / Copyright

Affiliations: Department of Internal Medicine 5, Hematology/Oncology, University of Erlangen-Nürnberg, Erlangen, Germany, INEM UMR 7355, CNRS and University Orléans, France
Pages: 2015-2020
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Published online on: March 10, 2014

https://doi.org/10.3892/or.2014.3070
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Abstract

The immune system contributes to tumor cell killing which can be enhanced by cancer chemotherapeutics and immune modulatory pharmaceuticals such as tyrosine kinase inhibitors (TKIs). Recently, the beneficial effect of natural killer (NK) cells was demonstrated when combining interleukin-2 (IL-2) with the TKI imatinib. The aim of the present study was to address the antitumor and immunological effects of recently approved TKIs. Therefore, we focused on the comparison of the efficacy between imatinib and nilotinib in combination with IL-2 in a murine B16F10 melanoma model. Both TKIs possessed antitumor activity in vivo. However, the combination of nilotinib and IL-2 showed a superior outcome. Importantly, both the use of immunodeficient Rag2γc-/- mice, which lack T-lymphocytes, B-lymphocytes and NK cells, as well as NK cell-depletion in C57Bl/6 mice reduced the therapeutic effect of nilotinib. Flow cytometry revealed a significant increase in the IFN-γ-producing CD27+ NK cell subpopulation following treatment with nilotinib and IL-2. Furthermore, the therapeutic antitumor effect of nilotinib/IL-2 was completely lost in IFN-γ-/- mice. In summary, we suggest that nilotinib combined with IL-2 confers high antitumor activity involving the subset of IFN-γ-producing CD27+ NK cells. These new insights are of high importance for the understanding and development of immunotherapeutic protocols using TKIs.

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Journals

International Journal of Molecular Medicine

International Journal of Oncology

Molecular Medicine Reports

Oncology Reports

Experimental and Therapeutic Medicine

Oncology Letters

Biomedical Reports

Molecular and Clinical Oncology

World Academy of Sciences Journal

International Journal of Functional Nutrition

International Journal of Epigenetics

Medicine International

Nilotinib combined with interleukin-2 mediates antitumor and immunological effects in a B16 melanoma model

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