title: Targeting KIT on innate immune cells to enhance the antitumor activity of checkpoint inhibitors.
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.
authors.affiliation: Department of Internal Medicine, Yale School of Medicine, 333 Cedar Street, New Haven, CT, USA.
authors.forename: Maximilian
authors.initials: M
authors.lastname: Stahl
authors.affiliation: Kolltan Pharmaceuticals, 300 George Street Suite 530, New Haven, CT, USA.
authors.forename: Richard
authors.initials: R
authors.lastname: Gedrich
authors.affiliation: Kolltan Pharmaceuticals, 300 George Street Suite 530, New Haven, CT, USA.
authors.forename: Ronald
authors.initials: R
authors.lastname: Peck
authors.affiliation: Kolltan Pharmaceuticals, 300 George Street Suite 530, New Haven, CT, USA.
authors.forename: Theresa
authors.initials: T
authors.lastname: LaVallee
authors.affiliation: Department of Medical Oncology & Yale Cancer Center, Yale School of Medicine, 333 Cedar Street, WWW211, New Haven, CT 06520, USA.
authors.forename: Joseph Paul
authors.initials: JP
authors.lastname: Eder
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D061025:Costimulatory and Inhibitory T-Cell Receptors / Q000037:antagonists & inhibitors; D004359:Drug Therapy, Combination; D006801:Humans; D007113:Immunity, Innate; D007167:Immunotherapy / Q000379:methods*; D058990:Molecular Targeted Therapy; D000072737:Myeloid-Derived Suppressor Cells / Q000276:immunology*; D009369:Neoplasms / Q000276:immunology / Q000628:therapy*; D019009:Proto-Oncogene Proteins c-kit / Q000378:metabolism*; D015398:Signal Transduction; D019139:Tumor Escape; D059016:Tumor Microenvironment
chemical_list: D000970:Antineoplastic Agents; D061025:Costimulatory and Inhibitory T-Cell Receptors; D019009:Proto-Oncogene Proteins c-kit
keywords: GIST; Ipilimumab; KIT receptor; KTN0158; immune checkpoint inhibitors; immunotherapy; mast cells; myeloid-derived suppressor cells; nivolumab; tumor microenvironment