ArticleJournal for immunotherapy of cancer2020
Enhanced antitumor immunity through sequential targeting of PI3Kδ and LAG3.
Article in Journal for immunotherapy of cancer, 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.
What it found
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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, 38 citations in OpenAlex.
- Safety and efficacy of dual PI3K-δ, γ inhibitor, duvelisib in patients with relapsed or refractory lymphoid neoplasms: A systematic review and meta-analysis of prospective clinical trials.Frontiers in immunology · 2022Pooled it
- Article
- Optimizing anti-PI3Kδ and anti-LAG-3 immunotherapy dosing regimens in a mouse model of triple-negative breast cancer improves outcome by removing treatment-related adverse events.Journal for immunotherapy of cancer · 2026Article
- Metabolic Reprogramming in Gastric Cancer Immunity Mechanisms and Therapeutic Implications.Oncology research · 2026Review
- Loss of PI3Kδ Activity Drives Autoimmune Colitis by Impairing Extrathymic Treg Differentiation.European journal of immunology · 2025Article
- LAG3 limits regulatory T cell proliferation in α-synuclein gut-to-brain transmission model.Journal of neuroinflammation · 2025Article
- Immune regeneration: implications for cancer immunotherapy and beyond.The Journal of clinical investigation · 2025Review
- Review
- Phase Ib study of the oral PI3Kδ inhibitor linperlisib in patients with advanced solid tumors.International journal of clinical oncology · 2025Article
- Pipelines for lymphocyte homeostasis maintenance during cancer immunotherapy.Frontiers in immunology · 2025Review
- Targeting the tumour vasculature: from vessel destruction to promotion.Nature reviews. Cancer · 2024Review
- LAG-3 : recent developments in combinational therapies in cancer.Cancer science · 2024Review
- Progressively Enhancing Stemness of Adoptively Transferred T Cells with PI3Kδ Blockade Improves Metabolism and Antitumor Immunity.Cancer research · 2024Article
- Tumor nano-lysate activates dendritic cells to evoke a preventative immune response.Journal of immunological methods · 2024Article
- Genetic dysregulation of immunologic and oncogenic signaling pathways associated with tumor-intrinsic immune resistance: a molecular basis for combination targeted therapy-immunotherapy for cancer.Cellular and molecular life sciences : CMLS · 2023Review
- The link between T cell activation and development of functionally useful tumour-associated high endothelial venules.Discovery immunology · 2023Review
- Three-dimensional Imaging Reveals Immune-driven Tumor-associated High Endothelial Venules as a Key Correlate of Tumor Rejection Following Depletion of Regulatory T Cells.Cancer research communications · 2022Article
- Article
- Cutting Edge: Promoting T Cell Factor 1Journal of immunology (Baltimore, Md. : 1950) · 2022Article
- Development of New Thiophene-Containing Triaryl Pyrazoline Derivatives as PI3Kγ Inhibitors.Molecules (Basel, Switzerland) · 2022Article
Corrections and comments
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Authors and funding
18 authors at 4 institutions in 1 country.
Funding
Abstract
backgroundDespite striking successes, immunotherapies aimed at increasing cancer-specific T cell responses are unsuccessful in most patients with cancer. Inactivating regulatory T cells (Treg) by inhibiting the PI3Kδ signaling enzyme has shown promise in preclinical models of tumor immunity and is currently being tested in early phase clinical trials in solid tumors.
methodsMice bearing 4T1 mammary tumors were orally administered a PI3Kδ inhibitor (PI-3065) daily and tumor growth, survival and T cell infiltrate were analyzed in the tumor microenvironment. A second treatment schedule comprised PI3Kδ inhibitor with anti-LAG3 antibodies administered sequentially 10 days later.
resultsAs observed in human immunotherapy trials with other agents, immunomodulation by PI3Kδ-blockade led to 4T1 tumor regressor and non-regressor mice. Tumor infiltrating T cells in regressors were metabolically fitter than those in non-regressors, with significant enrichments of antigen-specific CD8
conclusionsThese data indicate that LAG3 is a key bottleneck to successful PI3Kδ-targeted immunotherapy and provide a rationale for combining PI3Kδ/LAG3 blockade in future clinical studies.
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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 Socratic graph.