ArticlePloS one2012
PI3Kδ is essential for tumor clearance mediated by cytotoxic T lymphocytes.
Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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
28 citing papers in PubMed, 34 citations in OpenAlex.
- Homozygous Loss of Function PIK3CD Mutation in Multiple Siblings Leading To B Cell Dysregulation and Autoimmunity.Journal of clinical immunology · 2025Article
- Cell-type-specific requirement for TYK2 in murine immune cells under steady state and challenged conditions.Cellular and molecular life sciences : CMLS · 2025Article
- CD4Frontiers in immunology · 2025Review
- Inhibition of the PI3K/AKT/mTOR pathway in pancreatic cancer: is it a worthwhile endeavor?Therapeutic advances in medical oncology · 2024Review
- PI3K Isoform Immunotherapy for Solid Tumours.Current topics in microbiology and immunology · 2022Review
- Review
- Review
- PI3Kδ inhibition modulates regulatory and effector T-cell differentiation and function in chronic lymphocytic leukemia.Leukemia · 2019Article
- Phosphoinositide 3-kinase δ inhibition promotes antitumor responses but antagonizes checkpoint inhibitors.JCI insight · 2018Article
- Article
- Phosphoinositide 3-Kinase Signaling Pathway in Pancreatic Ductal Adenocarcinoma Progression, Pathogenesis, and Therapeutics.Frontiers in physiology · 2018Review
- Inhibition of PI4K IIIα radiosensitizes in human tumor xenograft and immune-competent syngeneic murine tumor model.Oncotarget · 2017Article
- Review
- PI3Kδ and primary immunodeficiencies.Nature reviews. Immunology · 2016Review
- Targeting PI3K in Cancer: Impact on Tumor Cells, Their Protective Stroma, Angiogenesis, and Immunotherapy.Cancer discovery · 2016Review
- Phosphatidylinositol 3-Kinase p110δ Isoform Regulates CD8+ T Cell Responses during Acute Viral and Intracellular Bacterial Infections.Journal of immunology (Baltimore, Md. : 1950) · 2016Article
- Disrupted PI3K p110δ Signaling Dysregulates Maternal Immune Cells and Increases Fetal Mortality In Mice.Cell reports · 2015Article
- PI3Kδ Regulates the Magnitude of CD8+ T Cell Responses after Challenge with Listeria monocytogenes.Journal of immunology (Baltimore, Md. : 1950) · 2015Article
- MyeloidOncoimmunology · 2015Article
- Immunomodulation of Selective Naive T Cell Functions by p110δ Inactivation Improves the Outcome of Mismatched Cell Transplantation.Cell reports · 2015Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundPI3Kδ is a lipid kinase of the phosphoinositide 3-kinase class 1A family and involved in early signaling events of leukocytes regulating proliferation, differentiation and survival. Currently, several inhibitors of PI3Kδ are under investigation for the treatment of hematopoietic malignancies. In contrast to the beneficial effect of inhibiting PI3Kδ in tumor cells, several studies reported the requirement of PI3Kδ for the function of immune cells, such as natural killer and T helper cells. Cytotoxic T lymphocytes (CTLs) are essential for tumor surveillance. The scope of this study is to clarify the potential impact of PI3Kδ inhibition on the function of CTLs with emphasis on tumor surveillance. PRINCIPAL
findingsPI3Kδ-deficient mice develop significantly bigger tumors when challenged with MC38 colon adenocarcinoma cells. This defect is accounted for by the fact that PI3Kδ controls the secretory perforin-granzyme pathway as well as the death-receptor pathway of CTL-mediated cytotoxicity, leading to severely diminished cytotoxicity against target cells in vitro and in vivo in the absence of PI3Kδ expression. PI3Kδ-deficient CTLs express low mRNA levels of important components of the cytotoxic machinery, e.g. prf1, grzmA, grzmB, fasl and trail. Accordingly, PI3Kδ-deficient tumor-infiltrating CTLs display a phenotype reminiscent of naïve T cells (CD69(low)CD62L(high)). In addition, electrophysiological capacitance measurements confirmed a fundamental degranulation defect of PI3Kδ-/- CTLs.
conclusionOur results demonstrate that CTL-mediated tumor surveillance is severely impaired in the absence of PI3Kδ and predict that impaired immunosurveillance may limit the effectiveness of PI3Kδ inhibitors in long-term treatment.
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.