GEO series
PP2A Regulates Senescence and Immunogenicity in Medulloblastoma
GSE302307
Mus musculus; Homo sapiens
Expression profiling by high throughput sequencing
24 samples
Submitted 2026/04/11
Platform GPL24676Platform GPL24247
Summary
Medulloblastoma (MB) is the most common malignant pediatric brain tumor. Current treatments carry significant morbidity, and prognosis remains poor in subgroups with TP53 mutations or relapse, underscoring the need for new therapeutic strategies. Senescence is a tumor-suppressive program disrupted in MB. We hypothesized that restoring senescence through p53-independent mechanisms could be therapeutic. Here, we identify Protein Phosphatase 2A (PP2A) as a key regulator of senescence in MB. Genetic ablation of the PP2A catalytic subunit (PP2Ac) or knockdown of the regulatory subunit PP2A-B56α induces robust senescence in TP53-mutant MB models. Senescent PP2Ac-deficient cells show increased MHC-I expression and enhanced immunogenicity. In a syngeneic orthotopic model, PP2Ac loss prolongs survival in an immune- and CD8-dependent manner, indicating enhanced immune-mediated tumor clearance. Analysis of MB patient datasets links senescence signatures with improved survival, and integrative single-cell analysis reveals reduced PP2A activity in immunogenic senescent clusters. Although the PP2A inhibitor LB-100 is under clinical investigation, it fails to cross the blood-brain barrier. To overcome this, we developed a lipid nanoparticle (LNP) formulation delivering siRNA against PP2Ac. LNP-siPP2Ac efficiently silences PP2Ac in vitro and, when locally delivered in vivo, extends survival and increases tumor MHC-I expression. These findings establish PP2A as a central modulator of senescence and immunogenicity in MB and support a therapeutic strategy that induces tumor cell senescence and enhances anti-tumor immunity for treatment of MB.
Published in
Ho WS, Mondal I, Liu J et al.
· The Journal of clinical investigation 2026
· PMID 42085538
· doi:10.1172/JCI196753
This dataset
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Direct links to NCBI, no account and no request form: the whole study as GSE302307_RAW.tar, processed values as the series matrix, the supplementary file directory, and per-sample supplementary files for any of the 24 samples. Raw sequencing reads are also available from ENA.
Also filed as BioProject PRJNA1289839 and SRA study SRP600913. Searching any of these in the dataset finder brings you back here.
Study design
8 conditions, mostly in triplicate
D425_PP2A_KO_NT ×3
D425_PP2A_KO_RT ×3
D425_PP2A_WT_NT ×3
D425_PP2A_WT_RT ×3
SJ_PP2A_WT ×3
SJ_PP2A_KO ×3
CTD_PP2A_WT ×3
CTD_PP2A_KO ×3
Supports a between-group comparison across 24 samples.
8 replicated groups read from 24 sample titles; they account for 24 of them. Check it against the sample list below before relying on it.
Samples in this study
0 selected
- GSM9101642 D425_PP2A_KO_NT_rep1
- GSM9101643 D425_PP2A_KO_NT_rep2
- GSM9101644 D425_PP2A_KO_NT_rep3
- GSM9101645 D425_PP2A_KO_RT_rep1
- GSM9101646 D425_PP2A_KO_RT_rep2
- GSM9101647 D425_PP2A_KO_RT_rep3
- GSM9101648 D425_PP2A_WT_NT_rep1
- GSM9101649 D425_PP2A_WT_NT_rep2
- GSM9101650 D425_PP2A_WT_NT_rep3
- GSM9101651 D425_PP2A_WT_RT_rep1
- GSM9101652 D425_PP2A_WT_RT_rep2
- GSM9101653 D425_PP2A_WT_RT_rep3
- GSM9101654 SJ_PP2A_WT_rep1
- GSM9101655 SJ_PP2A_WT_rep2
- GSM9101656 SJ_PP2A_WT_rep3
- GSM9101657 SJ_PP2A_KO_rep1
- GSM9101658 SJ_PP2A_KO_rep2
- GSM9101659 SJ_PP2A_KO_rep3
- GSM9581751 CTD_PP2A_WT_rep1
- GSM9581752 CTD_PP2A_WT_rep2
- GSM9581753 CTD_PP2A_WT_rep3
- GSM9581754 CTD_PP2A_KO_rep1
- GSM9581755 CTD_PP2A_KO_rep2
- GSM9581756 CTD_PP2A_KO_rep3
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