Open AccessInhibition of protein phosphatase-2A with LB-100 enhances antitumor immunity against glioblastoma
Author(s) -
Dominic Maggio,
Winson Ho,
Rebecca Breese,
Stuart Walbridge,
Herui Wang,
Jing Cui,
John D. Heiss,
Mark R. Gilbert,
John S. Kovach,
Rongze Lu,
Zhuang Zhang
Publication year - 2020
Publication title -
journal of neuro-oncology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.256
H-Index - 114
eISSN - 1573-7373
pISSN - 0167-594X
DOI - 10.1007/s11060-020-03517-5
Subject(s) - blockade , glioma , cancer research , immunotherapy , medicine , protein phosphatase 2 , cd8 , immune checkpoint , combination therapy , immune system , immunology , phosphatase , pharmacology , biology , receptor , phosphorylation , biochemistry
Glioblastoma (GBM) carries a dismal prognosis despite standard multimodal treatment with surgery, chemotherapy and radiation. Immune checkpoint inhibitors, such as PD1 blockade, for treatment of GBM failed to show clinical benefit. Rational combination strategies to overcome resistance of GBM to checkpoint monotherapy are needed to extend the promise of immunotherapy to GBM management. Emerging evidence suggests that protein phosphatase 2A (PP2A) plays a critical role in the signal transduction pathways of both adaptive and innate immune cells and that inhibition of PP2A could enhance cancer immunity. We investigated the use of a PP2A inhibitor, LB-100, to enhance antitumor efficacy of PD1 blockade in a syngeneic glioma model.