ArticleJournal of neuro-oncology2020
Inhibition of protein phosphatase-2A with LB-100 enhances antitumor immunity against glioblastoma.
Article in Journal of neuro-oncology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers, 1 of them a synthesis that pooled it.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
24 citing papers in PubMed, 1 synthesis or guideline pooled it, 33 citations in OpenAlex.
- cGAS-STING agonists in preclinical glioblastoma animal models: a systematic review of tumor microenvironment modulation and survival outcomes.Journal of neuro-oncology · 2026Pooled it
- Protein phosphatase 2A regulates senescence and immunogenicity in medulloblastoma models.The Journal of clinical investigation · 2026Article
- PPP2R2C confers radioresistance in nasopharyngeal carcinoma by suppressing ferroptosis via RPS27L stabilization.Cell death & disease · 2026Article
- On the history, synthesis, and medicinal use of cantharidin, LB-100, and their analogs.RSC medicinal chemistry · 2026Review
- Macrophages in tumors with downregulated MHC-I expression: emerging therapeutic opportunities and translational challenges.Clinical and experimental immunology · 2026Review
- MYC at the tumor-immune interface: mechanisms of immune escape and immunotherapy resistance.Frontiers in immunology · 2026Review
- An AMBRA1, ULK1 and PP2A regulatory network regulates cytotoxic T cell differentiation via TFEB activation.Scientific reports · 2024Article
- Co-evolution of glioma and immune microenvironment.Journal for immunotherapy of cancer · 2024Review
- A combination of protein phosphatase 2A inhibition and checkpoint immunotherapy: a perfect storm.Molecular oncology · 2024Review
- The phosphatase inhibitor LB-100 creates neoantigens in colon cancer cells through perturbation of mRNA splicing.EMBO reports · 2024Article
- Glioma-Immune Cell Crosstalk in Tumor Progression.Cancers · 2024Review
- A Small Molecule Inhibitor of Leucine Carboxyl Methyltransferase-1 Inhibits Cancer Cell Survival.Frontiers in drug discovery · 2024Article
- An LC-MS/MS method for simultaneous determination of LB-100 and its active metabolite, endothall, in human plasma.Bioanalysis · 2023Article
- Protein Phosphatase 2A as a Therapeutic Target in Pulmonary Diseases.Medicina (Kaunas, Lithuania) · 2023Review
- PP2Ac Deficiency Enhances Tumor Immunogenicity by Activating STING-Type I Interferon Signaling in Glioblastoma.Cancer research · 2023Article
- Targeting protein phosphatases in cancer immunotherapy and autoimmune disorders.Nature reviews. Drug discovery · 2023Review
- PP2Ac/STRN4 negatively regulates STING-type I IFN signaling in tumor-associated macrophages.The Journal of clinical investigation · 2023Article
- The Pivotal Role of Protein Phosphatase 2A (PP2A) in Brain Tumors.International journal of molecular sciences · 2022Review
- Targeting PP2A for cancer therapeutic modulation.Cancer biology & medicine · 2022Review
- Review
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 1 country.
Funding
Abstract
purposeGlioblastoma (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.
methodsC57BL/6 mice were implanted with murine glioma cell line GL261-luc or GL261-WT and randomized into 4 treatment arms: (i) control, (ii) LB-100, (iii) PD1 blockade and (iv) combination. Survival was assessed and detailed profiling of tumor infiltrating leukocytes was performed.
resultsDual PP2A and PD1 blockade significantly improved survival compared with monotherapy alone. Combination therapy resulted in complete regression of tumors in about 25% of mice. This effect was dependent on CD4 and CD8 T cells and cured mice established antigen-specific secondary protective immunity. Analysis of tumor lymphocytes demonstrated enhanced CD8 infiltration and effector function.
conclusionThis is the first preclinical investigation of the effect of combining PP2A inhibition with PD1 blockade for GBM. This novel combination provided effective tumor immunotherapy and long-term survival in our animal GBM model.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.