Stahl Maximilian, Gedrich Richard, Peck Ronald, LaVallee Theresa, Eder Joseph Paul
Department of Internal Medicine, Yale School of Medicine, 333 Cedar Street, New Haven, CT, USA.
Kolltan Pharmaceuticals, 300 George Street Suite 530, New Haven, CT, USA.
Immunotherapy. 2016 Jun;8(7):767-74. doi: 10.2217/imt-2016-0040.
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.
诸如肥大细胞和髓源性抑制细胞等固有免疫细胞是肿瘤微环境的关键组成部分。最近的证据表明，黑色素瘤患者体内髓源性抑制细胞的水平与对检查点抑制剂的低生存率相关。这表明，针对免疫系统的固有和适应性抑制成分将使临床获益最大化，并在癌症患者中引发更持久的反应。临床前数据表明，靶向受体酪氨酸激酶KIT的信号传导，特别是在肥大细胞上的信号传导，可能会调节肿瘤中固有免疫细胞的数量和活性。在此，我们综述了强调KIT信号传导在调节抗肿瘤免疫反应中的重要性以及将选择性KIT抑制剂与免疫检查点抑制剂联合使用的潜在益处的数据。
