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Review
. 2016 Jun;8(7):767-74.
doi: 10.2217/imt-2016-0040.

Targeting KIT on Innate Immune Cells to Enhance the Antitumor Activity of Checkpoint Inhibitors

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Review

Targeting KIT on Innate Immune Cells to Enhance the Antitumor Activity of Checkpoint Inhibitors

Maximilian Stahl et al. Immunotherapy. .

Abstract

Innate immune cells such as mast cells and myeloid-derived suppressor cells are key components of the tumor microenvironment. Recent evidence indicates that levels of myeloid-derived suppressor cells in melanoma patients are associated with poor survival to checkpoint inhibitors. This suggests that targeting both the innate and adaptive suppressive components of the immune system will maximize clinical benefit and elicit more durable responses in cancer patients. Preclinical data suggest that targeting signaling by the receptor tyrosine kinase KIT, particularly on mast cells, may modulate innate immune cell numbers and activity in tumors. Here, we review data highlighting the importance of the KIT signaling in regulating antitumor immune responses and the potential benefit of combining selective KIT inhibitors with immune checkpoint inhibitors.

Keywords: GIST; Ipilimumab; KIT receptor; KTN0158; immune checkpoint inhibitors; immunotherapy; mast cells; myeloid-derived suppressor cells; nivolumab; tumor microenvironment.

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