Oh Taemin, Ivan Michael E, Sun Matthew Z, Safaee Michael, Fakurnejad Shayan, Clark Aaron J, Sayegh Eli T, Bloch Orin, Parsa Andrew T
Department of Neurological Surgery, Feinberg School of Medicine, Northwestern University, Feinberg School of Medicine, 676 N St Clair Street, Suite 2210, Chicago, IL 60611-2911, USA.
Immunotherapy. 2014;6(6):737-53. doi: 10.2217/imt.14.35.
Constitutive activation of the PI3K pathway has been implicated in glioblastoma (GBM) pathogenesis. Pharmacologic inhibition can both inhibit tumor survival and downregulate expression of programmed death ligand-1, a protein highly expressed on glioma cells that strongly contributes to cancer immunosuppression. In that manner, PI3K pathway inhibitors can help optimize GBM vaccine immunotherapy. In this review, we describe and assess the potential integration of various classes of PI3K pathway inhibitors into GBM immunotherapy. While early-generation inhibitors have a wide range of immunosuppressive effects that could negate their antitumor potency, further work should better characterize how contemporary inhibitors affect the immune response. This will help determine if these inhibitors are truly a therapeutic avenue with a strong future in GBM immunotherapy.
PI3K通路的组成性激活与胶质母细胞瘤（GBM）的发病机制有关。药物抑制既能抑制肿瘤存活，又能下调程序性死亡配体-1的表达，该蛋白在胶质瘤细胞上高度表达，对癌症免疫抑制有很大影响。通过这种方式，PI3K通路抑制剂有助于优化GBM疫苗免疫治疗。在这篇综述中，我们描述并评估了各类PI3K通路抑制剂与GBM免疫治疗潜在的整合情况。虽然早期抑制剂具有广泛的免疫抑制作用，可能会抵消其抗肿瘤效力，但进一步的研究应更好地阐明当代抑制剂如何影响免疫反应。这将有助于确定这些抑制剂是否真的是GBM免疫治疗中具有强大前景的治疗途径。
