ArticleCancer immunology research2016
Enhanced Tumor Control with Combination mTOR and PD-L1 Inhibition in Syngeneic Oral Cavity Cancers.
Article in Cancer immunology research, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 78 papers.
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Who cites it
78 citing papers in PubMed, 103 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
- Inhibition of mTOR Signaling and Clinical Activity of Rapamycin in Head and Neck Cancer in a Window of Opportunity Trial.Clinical cancer research : an official journal of the American Association for Cancer Research · 2019Trial
- Blueberry Extract Has Anti-Proliferative Activity in Preclinical Models of Head and Neck Cancer.Head & neck · 2026Article
- Uncovering the Potential of 3D Spheroids for Modeling the Cellular Crosstalk Within the Tumor Microenvironment in HNSCC.Biotechnology journal · 2026Review
- Loss of Kmt2c/d promotes gastric cancer and confers vulnerability to mTORC1 and PD-1 inhibition.The Journal of clinical investigation · 2026Article
- mTOR inhibition augments antitumor immune effector response by reprogramming thebioRxiv : the preprint server for biology · 2026Article
- Multifunctional Role of Mitochondrial Fatty Acid Oxidation in Cancer Immunotherapy and Aging.Cancer science · 2026Review
- Tumor implantation site dictates the immune landscape of syngeneic mouse models of head and neck cancer.Scientific reports · 2026Article
- TGFβ limits proximal CD8+ TCR signaling via PTPN22 following strong and moderate agonism.Journal of immunology (Baltimore, Md. : 1950) · 2025Article
- Article
- Cancer Cell-Intrinsic Type I Interferon Signaling Promotes Antitumor Immunity in Head and Neck Squamous Cell Carcinoma.Cancers · 2025Article
- Analyzing research trends in the relationship between immunosuppressants and cancer following organ transplantation: a bibliometric study from 2001 to 2023.Discover oncology · 2025Article
- Immune-metabolic crosstalk in HNSCC: mechanisms and therapeutic opportunities.Frontiers in oncology · 2025Review
- Alum-anchored IL-12 combined with cytotoxic chemotherapy and immune checkpoint blockade enhanced antitumor immune responses in head and neck cancer models.Journal for immunotherapy of cancer · 2024Article
- Article
- TGF-β neutralization attenuates tumor residency of activated T cells to enhance systemic immunity in mice.iScience · 2024Article
- Characterization of the tumor microenvironment in the mouse oral cancer (MOC1) model after orthotopic implantation in the buccal mucosa.Head & neck · 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
- Article
- New insights into RAS in head and neck cancer.Biochimica et biophysica acta. Reviews on cancer · 2023Review
18 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 4 institutions in 1 country.
Funding
Abstract
Significant subsets of patients with oral cancer fail to respond to single-agent programmed death (PD) blockade. Syngeneic models of oral cancer were used to determine if blocking oncogenic signaling improved in vivo responses to PD-L1 monoclonal antibody (mAb). Anti-PD-L1 enhanced durable primary tumor control and survival when combined with mTOR (rapamycin), but not in combination with MEK inhibition (PD901) in immunogenic MOC1 tumors. Conversely, PD-L1 mAb did not enhance tumor control in poorly immunogenic MOC2 tumors. Rapamycin enhanced expansion of peripheral antigen-specific CD8 T cells and IFNγ production following ex vivo antigen stimulation. More CD8 T cells infiltrated and were activated after PD-L1 mAb treatment in mice with immunogenic MOC1 tumors, which were stable or increased by the addition of rapamycin, but suppressed when PD901 was added. Rapamycin increased IFNγ production capacity in peripheral and tumor-infiltrating CD8 T cells. In vivo antibody depletion revealed a CD8 T-cell-dependent, and not NK cell-dependent mechanism of tumor growth inhibition after treatment with rapamycin and PD-L1 mAb, ruling out significant effects from NK cell-mediated antibody-dependent cellular cytotoxicity. Rapamycin also enhanced IFNγ or PD-L1 mAb treatment-associated induction of MHC class I expression on MOC1 tumor cells, an effect abrogated by depleting infiltrating CD8 T cells from the tumor microenvironment. These data conflict with traditional views of rapamycin as a universal immunosuppressant, and when combined with evidence of enhanced antitumor activity with the combination of rapamycin and PD-L1 mAb, suggest that this treatment combination deserves careful evaluation in the clinical setting. Cancer Immunol Res; 4(7); 611-20. ©2016 AACR.
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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.