ArticleOncoimmunology
Combination of dual mTORC1/2 inhibition and immune-checkpoint blockade potentiates anti-tumour immunity.
Article in Oncoimmunology. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed, 52 citations in OpenAlex.
- Multicenter phase 1/2 study of onatasertib, a dual TORC1/2 inhibitor, combined with the PD-1 antibody toripalimab in advanced solid tumors.Signal transduction and targeted therapy · 2025Trial
- Aging and cancer: current understandings and future perspectives.Signal transduction and targeted therapy · 2026Review
- TP53 Loss Fuels mTORC1 Activation and Autophagy Suppression to Drive Immune-Cold Colorectal Cancer.World journal of oncology · 2026Article
- Ole-4, a novel synthetic derivative of Oleuropein, enhances antitumor immunity and modulates kinase activity-dependent signaling.Journal of translational medicine · 2026Article
- Revitalizing T cells: breakthroughs and challenges in overcoming T cell exhaustion.Signal transduction and targeted therapy · 2026Review
- Onatasertib re-sensitizes refractory nasopharyngeal carcinoma to immunotherapy: a Case Report.Frontiers in pharmacology · 2026Article
- The role of the tumour microenvironment in lung cancer and its therapeutic implications.Medical oncology (Northwood, London, England) · 2025Review
- Targeting metabolic dysfunction of CD8 T cells and natural killer cells in cancer.Nature reviews. Drug discovery · 2025Review
- Targeting myeloid cells to improve cancer immune therapy.Frontiers in immunology · 2025Review
- PI3K/mTOR inhibition induces tumour microenvironment remodelling and sensitises pS6Clinical and translational medicine · 2024Article
- Primary prophylaxis with mTOR inhibitor enhances T cell effector function and prevents heart transplant rejection during talimogene laherparepvec therapy of squamous cell carcinoma.Nature communications · 2024Article
- Applications of Flow Cytometry in Drug Discovery and Translational Research.International journal of molecular sciences · 2024Review
- Unlocking the potential of T-cell metabolism reprogramming: Advancing single-cell approaches for precision immunotherapy in tumour immunity.Clinical and translational medicine · 2024Review
- Case report: Sustained complete remission with all-oral MEPED therapy in a patient with Hodgkin's disease developing resistance to pembrolizumab.Frontiers in pharmacology · 2024Article
- Enhanced bypass of PD-L1 translation reduces the therapeutic response to mTOR kinase inhibitors.Cell reports · 2023Article
- Exploring the mTOR Signalling Pathway and Its Inhibitory Scope in Cancer.Pharmaceuticals (Basel, Switzerland) · 2023Review
- Immunosuppression for immune-related adverse events during checkpoint inhibition: an intricate balance.NPJ precision oncology · 2023Review
- 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
- Targeting mTOR as a Cancer Therapy: Recent Advances in Natural Bioactive Compounds and Immunotherapy.Cancers · 2022Review
- Article
Corrections and comments
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Authors and funding
11 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
mTOR inhibition can promote or inhibit immune responses in a context dependent manner, but whether this will represent a net benefit or be contraindicated in the context of immunooncology therapies is less understood. Here, we report that the mTORC1/2 dual kinase inhibitor vistusertib (AZD2014) potentiates anti-tumour immunity in combination with anti-CTLA-4 (αCTLA-4), αPD-1 or αPD-L1 immune checkpoint blockade. Combination of vistusertib and immune checkpoint blocking antibodies led to tumour growth inhibition and improved survival of MC-38 or CT-26 pre-clinical syngeneic tumour models, whereas monotherapies were less effective. Underlying these combinatorial effects, vistusertib/immune checkpoint combinations reduced the occurrence of exhausted phenotype tumour infiltrating lymphocytes (TILs), whilst increasing frequencies of activated Th1 polarized T-cells in tumours. Vistusertib alone was shown to promote a Th1 polarizing proinflammatory cytokine profile by innate primary immune cells. Moreover, vistusertib directly enhanced activation of effector T-cell and survival, an effect that was critically dependent on inhibitor dose. Therefore, these data highlight direct, tumour-relevant immune potentiating benefits of mTOR inhibition that complement immune checkpoint blockade. Together, these data provide a clear rationale to investigate such combinations in the clinic.
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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.