ArticleMolecular cancer therapeutics2014
Blockade of mTOR signaling via rapamycin combined with immunotherapy augments antiglioma cytotoxic and memory T-cell functions.
Article in Molecular cancer therapeutics, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 52 citations in OpenAlex.
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- Metabolic reprogramming in cancer: signaling pathways and therapeutic targets.Molecular cancer · 2026Review
- Regulators of CD8Nature reviews. Immunology · 2026Review
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- A novel strategy to fuel cancer immunotherapy: targeting glucose metabolism to remodel the tumor microenvironment.Frontiers in oncology · 2022Review
- Emerging role of metabolic reprogramming in tumor immune evasion and immunotherapy.Science China. Life sciences · 2021Review
- mTOR-targeted cancer therapy: great target but disappointing clinical outcomes, why?Frontiers of medicine · 2021Review
- Inhibition of 2-hydroxyglutarate elicits metabolic reprogramming and mutant IDH1 glioma immunity in mice.The Journal of clinical investigation · 2021Article
- Metabolic interventions: A new insight into the cancer immunotherapy.Archives of biochemistry and biophysics · 2021Review
- Mechanistic Target of Rapamycin Inhibitors in Renal Cell Carcinoma: Potential, Limitations, and Perspectives.Frontiers in cell and developmental biology · 2021Review
- Nanomaterials Enhance the Immunomodulatory Effect of Molecular Targeted Therapy.International journal of nanomedicine · 2021Review
- Immunocompetent Mouse Models in the Search for Effective Immunotherapy in Glioblastoma.Cancers · 2020Review
- Searching for the real function of mTOR signaling in the regulation of PD-L1 expression.Translational oncology · 2020Review
- A review of cancer immunotherapy: from the past, to the present, to the future.Current oncology (Toronto, Ont.) · 2020Review
- Competitive glucose metabolism as a target to boost bladder cancer immunotherapy.Nature reviews. Urology · 2020Review
- Article
- Article
- PTEN expression by an oncolytic herpesvirus directs T-cell mediated tumor clearance.Nature communications · 2018Article
- Tumor Microenvironment-Induced Immunometabolic Reprogramming of Natural Killer Cells.Frontiers in immunology · 2018Review
- Production of interleukin-1β related to mammalian target of rapamycin/Toll-like receptor 4 signaling pathway duringInternational journal of ophthalmology · 2018Article
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
The success of immunotherapeutic approaches targeting glioblastoma multiforme (GBM) demands a robust antiglioma T-cell cytotoxic and memory response. Recent evidence suggests that rapamycin regulates T-cell differentiation. Herein, we tested whether administration of rapamycin could enhance the efficacy of immunotherapy utilizing Fms-like tyrosine kinase 3 ligand (Ad-Flt3L) and thymidine kinase/ganciclovir (Ad-TK/GCV). Using the refractory rat RG2 glioma model, we demonstrate that administration of rapamycin with Ad-Flt3L + Ad-TK/GCV immunotherapy enhanced the cytotoxic activity of antitumor CD8(+) T cells. Rats treated with rapamycin + Ad-Flt3L + Ad-TK/GCV exhibited massive reduction in the tumor volume and extended survival. Rapamycin administration also prolonged the survival of Ad-Flt3L + Ad-TK/GCV-treated GL26 tumor-bearing mice, associated with an increase in the frequency of tumor-specific and IFNγ(+) CD8(+) T cells. More importantly, rapamycin administration, even for a short interval, elicited a potent long-lasting central memory CD8(+) T-cell response. The enhanced memory response translated to an increased frequency of tumor-specific CD8(+) T cells within the tumor and IFNγ release, providing the mice with long-term survival advantage in response to tumor rechallenge. Our data, therefore, point to rapamycin as an attractive adjuvant to be used in combination with immunotherapy in a phase I clinical trial for GBM.
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