ArticleEuropean journal of immunology2020
Ex vivo blockade of PI3K gamma or delta signaling enhances the antitumor potency of adoptively transferred CD8
Article in European journal of immunology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.
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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
48 citing papers in PubMed, 61 citations in OpenAlex.
- Phase I/II clinical trial of temsirolimus and lenalidomide in patients with relapsed and refractory lymphomas.Haematologica · 2022Trial
- PI3Kγ inhibition drives M1 macrophage differentiation and synergizes with PD-L1 blockade to improve survival in poorly immunogenic head and neck squamous cell carcinoma.Cancer biology & therapy · 2026Article
- The PI3Kδ inhibitor roginolisib (IOA-244) preserves T-cell function and activity.Molecular oncology · 2026Article
- PI3Kδ inhibition alters CD8 T cell differentiation and reprograms the tumor microenvironment following adoptive immunotherapy.Journal of immunology (Baltimore, Md. : 1950) · 2026Article
- Spatiotemporal dynamics of adoptively transferred stem-like CD8bioRxiv : the preprint server for biology · 2026Article
- Redox index and capacity analysis (RICA) reveals NAD biology changes in T cell responses in vitro and ex vivo.Journal of immunology (Baltimore, Md. : 1950) · 2026Article
- Combining Small-Molecular Compounds With CAR T-Cell Therapy: Novel Strategies for Enhanced Cancer Immunotherapy.Cancer innovation · 2026Review
- Mechanistic basis and therapeutic modulation of T cell fitness to enhance CAR-T cell efficacy in hematological malignancies.Frontiers in immunology · 2026Review
- AMPK agonism optimizes the in vivo activation and antileukemic efficacy of chimeric antigen receptor T cells.Journal for immunotherapy of cancer · 2025Article
- The science of tumor-infiltrating lymphocytes (TIL): perspectives from the SITC Surgery Committee.Journal for immunotherapy of cancer · 2025Review
- Article
- A New Method of Canine CD4International journal of molecular sciences · 2025Article
- Novel strategies to manage CAR-T cell toxicity.Nature reviews. Drug discovery · 2025Review
- Metabolic reprogramming of CAR T cells: a new frontier in cancer immunotherapy.Frontiers in immunology · 2025Review
- Dysregulated tryptophan metabolism: driving T cell subsets and PI3K-Akt pathway alterations in Hashimoto's thyroiditis.Frontiers in immunology · 2025Article
- PI3K/AKT/mTOR and PD‑1/CTLA‑4/CD28 pathways as key targets of cancer immunotherapy (Review).Oncology letters · 2024Review
- CD28 co-stimulation: novel insights and applications in cancer immunotherapy.Nature reviews. Immunology · 2024Review
- Review
- Fueling CARs: metabolic strategies to enhance CAR T-cell therapy.Experimental hematology & oncology · 2024Review
- From complexity to clarity: unravelling tumor heterogeneity through the lens of tumor microenvironment for innovative cancer therapy.Histochemistry and cell biology · 2024Review
Corrections and comments
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Authors and funding
11 authors at 1 institution in 1 country.
Funding
Abstract
Adoptive T cell transfer therapy induces objective responses in patients with advanced malignancies. Despite these results, some individuals do not respond due to the generation of terminally differentiated T cells during the expansion protocol. As the gamma and delta catalytic subunits in the PI3K pathway are abundant in leukocytes and involved in cell activation, we posited that blocking both subunits ex vivo with the inhibitor IPI-145 would prevent their differentiation, thereby increasing antitumor activity in vivo. However, IPI-145 treatment generated a product with reduced antitumor activity. Instead, T cells inhibited of PI3Kγ (IPI-549) or PI3Kδ (CAL-101 or TGR-1202) alone were more potent in vivo. While T cells coinhibited of PI3Kγ and PI3Kδ were less differentiated, they were functionally impaired, indicated by reduced production of effector cytokines after antigenic re-encounter and decreased persistence in vivo. Human CAR T cells expanded with either a PI3Kγ or PI3Kδ inhibitor possessed a central memory phenotype compared to vehicle cohorts. We also found that PI3Kδ-inhibited CARs lysed human tumors in vitro more effectively than PI3Kγ-expanded or traditionally expanded CAR T cells. Our data imply that sole blockade of PI3Kγ or PI3Kδ generates T cells with remarkable antitumor properties, a discovery that has substantial clinical implications.
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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.