ArticleJournal for immunotherapy of cancer2022
MEK1/2 inhibition transiently alters the tumor immune microenvironment to enhance immunotherapy efficacy against head and neck cancer.
Article in Journal for immunotherapy of cancer, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 67 citations in OpenAlex.
- Physical Exercise in Immunotherapy.Sports medicine - open · 2026Review
- Exercise and CD8Journal of molecular medicine (Berlin, Germany) · 2026Review
- Overcoming resistance to anti-PD-1/PD-L1 therapy in cancer.Cancer drug resistance (Alhambra, Calif.) · 2026Review
- Cross-disciplinary communication between oral and gut microbiota in head and neck cancer.Frontiers in oncology · 2026Review
- Hypoxia-induced EGR1 remodels neutrophils to suppress antitumor immunity.Science immunology · 2025Article
- MET pathway inhibition increases chemo-immunotherapy efficacy in small cell lung cancer.Cell reports. Medicine · 2025Article
- A heterogeneous pharmaco-transcriptomic landscape induced by targeting a single oncogenic kinase.bioRxiv : the preprint server for biology · 2025Article
- Gene mutations and differentiation in laryngeal and pharyngeal squamous cell carcinoma.Discover oncology · 2025Article
- Cancer neuroscience in head and neck: interactions, modulation, and therapeutic strategies.Molecular cancer · 2025Review
- NR2F6 promotes the malignant progression of neuroblastoma as an indicator of poor prognosis.PloS one · 2025Article
- Itaconate targets the ERK2 signal to suppress estrogen receptor-positive breast cancer cell growth.American journal of cancer research · 2025Article
- Dual inhibition of HERs and PD-1 counteract resistance in KRASJournal of experimental & clinical cancer research : CR · 2024Article
- MAP kinase kinase 1 (MEK1) within extracellular vesicles inhibits tumour growth by promoting anti-tumour immunity.Journal of extracellular vesicles · 2024Article
- Emerging Targets in Non-Small Cell Lung Cancer.International journal of molecular sciences · 2024Review
- A novel pan-PI3K inhibitor KTC1101 synergizes with anti-PD-1 therapy by targeting tumor suppression and immune activation.Molecular cancer · 2024Article
- ERK pathway agonism for cancer therapy: evidence, insights, and a target discovery framework.NPJ precision oncology · 2024Review
- Trametinib ameliorates aging-associated gut pathology inProceedings of the National Academy of Sciences of the United States of America · 2024Article
- Activation of the EGFR/PI3K/AKT pathway limits the efficacy of trametinib treatment in head and neck cancer.Molecular oncology · 2023Article
- New insights into RAS in head and neck cancer.Biochimica et biophysica acta. Reviews on cancer · 2023Review
- Drug Repurposing to Circumvent Immune Checkpoint Inhibitor Resistance in Cancer Immunotherapy.Pharmaceutics · 2023Review
Corrections and comments
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Authors and funding
32 authors at 6 institutions in 5 countries.
Funding
Abstract
backgroundAlthough the mitogen-activated protein kinases (MAPK) pathway is hyperactive in head and neck cancer (HNC), inhibition of MEK1/2 in HNC patients has not shown clinically meaningful activity. Therefore, we aimed to characterize the effect of MEK1/2 inhibition on the tumor microenvironment (TME) of MAPK-driven HNC, elucidate tumor-host interaction mechanisms facilitating immune escape on treatment, and apply rationale-based therapy combination immunotherapy and MEK1/2 inhibitor to induce tumor clearance.
methodsMouse syngeneic tumors and xenografts experiments were used to analyze tumor growth in vivo. Single-cell cytometry by time of flight, flow cytometry, and tissue stainings were used to profile the TME in response to trametinib (MEK1/2 inhibitor). Co-culture of myeloid-derived suppressor cells (MDSC) with CD8
resultsUsing preclinical HNC models, we demonstrated that treatment with trametinib delays HNC initiation and progression by reducing tumor cell proliferation and enhancing the antitumor immunity of CD8
conclusionOur findings provide the rationale for testing the trametinib/αPD-1 combination in HNC and highlight the importance of sensitizing tumors to αPD-1 by using MEK1/2 to interfere with the tumor-host interaction. Moreover, we describe the concept that treatment of cancer with a targeted therapy transiently induces an immune-active microenvironment, and supplementation of immunotherapy during this time further activates the antitumor machinery to cause tumor elimination.
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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.