ArticleProceedings of the National Academy of Sciences of the United States of America2021
PI3Kγ inhibition suppresses microglia/TAM accumulation in glioblastoma microenvironment to promote exceptional temozolomide response.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 64 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
64 citing papers in PubMed, 1 synthesis or guideline pooled it, 82 citations in OpenAlex.
- Targeting PI3K-gamma in myeloid driven tumour immune suppression: a systematic review and meta-analysis of the preclinical literature.Cancer immunology, immunotherapy : CII · 2024Pooled it
- Integrative multi-omics analysis and machine learning identify M2 macrophage-induced ferroptosis resistance in glioblastoma.Functional & integrative genomics · 2026Article
- Glioblastoma: epidemiology, molecular pathogenesis, diagnosis, management, and therapeutic resistance.Molecular biomedicine · 2026Review
- Molecular immune signature identifies microglia and NK cell infiltration as a favorable prognostic marker in adult-type high-grade glioma.ESMO open · 2026Article
- Valproic acid reverses macrophage-mediated temozolomide resistance in macrophage-rich gliomas.NPJ precision oncology · 2026Article
- 3D heterotypic models of glioblastoma reveal the impact of microglia on cellular organization and the production of a distinct secretome.Scientific reports · 2026Article
- Neuro-Immune Crosstalk: Molecular Mechanisms, Biological Functions, Diseases, and Therapeutic Targets.MedComm · 2026Review
- Tumor-associated macrophage-specific LRRFIP1 promotes M2 macrophage polarization and progression of colorectal cancer via activation of the PI3K pathway.Journal of translational medicine · 2026Article
- CDK12 regulates cellular metabolism to promote glioblastoma growth.JCI insight · 2025Article
- Positive and negative roles of myeloid cells in cancer immunotherapy.Journal for immunotherapy of cancer · 2025Review
- PI3Kγ in Tumour Inflammation: Bridging Immune Response and Cancer Progression-A Mini-Review.Immunology · 2025Review
- Comprehensive Characterization of the Immune Microenvironment Based on Nested Resampling Machine Learning Framework Identifies TRAF3 Interacting Protein 3 as a Promising Regulator to Improve the Resistance to Immunotherapy in Glioma.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Review
- Therapeutic potential of targeting macrophages and microglia in glioblastoma.Trends in pharmacological sciences · 2025Review
- Article
- The Basis for Targeting the Tumor Macrophage Compartment in Glioblastoma Immunotherapy.Cancers · 2025Review
- Targeting PI3Kγ in cancer.Trends in cancer · 2025Review
- Targeting PI3K signaling in Lung Cancer: advances, challenges and therapeutic opportunities.Journal of translational medicine · 2025Review
- New Insights into Monocyte-Derived Macrophages in Glioblastoma.Research (Washington, D.C.) · 2025Review
- Targeting myeloid cells to improve cancer immune therapy.Frontiers in immunology · 2025Review
4 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
21 authors at 5 institutions in 2 countries.
Funding
Abstract
Precision medicine in oncology leverages clinical observations of exceptional response. Toward an understanding of the molecular features that define this response, we applied an integrated, multiplatform analysis of RNA profiles derived from clinically annotated glioblastoma samples. This analysis suggested that specimens from exceptional responders are characterized by decreased accumulation of microglia/macrophages in the glioblastoma microenvironment. Glioblastoma-associated microglia/macrophages secreted interleukin 11 (IL11) to activate STAT3-MYC signaling in glioblastoma cells. This signaling induced stem cell states that confer enhanced tumorigenicity and resistance to the standard-of-care chemotherapy, temozolomide (TMZ). Targeting a myeloid cell restricted an isoform of phosphoinositide-3-kinase, phosphoinositide-3-kinase gamma isoform (PI3Kγ), by pharmacologic inhibition or genetic inactivation disrupted this signaling axis by reducing microglia/macrophage-associated IL11 secretion in the tumor microenvironment. Mirroring the clinical outcomes of exceptional responders, PI3Kγ inhibition synergistically enhanced the anti-neoplastic effects of TMZ in orthotopic murine glioblastoma models. Moreover, inhibition or genetic inactivation of PI3Kγ in murine glioblastoma models recapitulated expression profiles observed in clinical specimens isolated from exceptional responders. Our results suggest key contributions from tumor-associated microglia/macrophages in exceptional responses and highlight the translational potential for PI3Kγ inhibition as a glioblastoma therapy.
Indexed as
Identifiers
What OpenQuestion holds
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.