ArticleNature communications2017
Agonist immunotherapy restores T cell function following MEK inhibition improving efficacy in breast cancer.
Article in Nature communications, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 84 papers.
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
84 citing papers in PubMed, 118 citations in OpenAlex.
- A Randomized Phase II Study of Combination Atezolizumab and Varlilumab (CDX-1127) with or without Cobimetinib in Previously Treated Unresectable Biliary Tract Cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2026Trial
- Combined MEK/PD-L1 Inhibition Alters Peripheral Cytokines and Lymphocyte Populations Correlating with Improved Clinical Outcomes in Advanced Biliary Tract Cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2022Trial
- Multicenter randomized phase II trial of atezolizumab with or without cobimetinib in biliary tract cancers.The Journal of clinical investigation · 2021Trial
- TGF-β1 drives neutrophil extracellular traps formation to promote CD8Journal for immunotherapy of cancer · 2026Article
- The MEK inhibitor trametinib incurs mitochondrial injury and induces innate immune responses in the mouse heart.Science advances · 2026Article
- Characterization of Circ_0048766: an oncogenic circular rna promoting triple-negative breast cancer progression via the miR-329-3p/CXCR4 axis and regulated by METTL3.Cancer cell international · 2026Article
- MEK inhibitor cobimetinib increases calreticulin and induces immune modulation in TNBC.Journal of molecular medicine (Berlin, Germany) · 2026Article
- Multi-tyrosine kinase inhibitors: exploring immunomodulatory effects on various immune cell types in cancer.Cancer cell international · 2026Review
- Prognostic analysis and immunotherapy prediction based on key receptor-ligand pairs of bladder cancer.Discover oncology · 2025Article
- The MEK inhibitor trametinib incurs mitochondrial injury and induces innate immune responses in the mouse heart.bioRxiv : the preprint server for biology · 2025Article
- Review
- A Phase 1/1B Trial of Pembrolizumab and Trametinib in Advanced NSCLC Enriched for KRAS Mutations.JTO clinical and research reports · 2025Article
- Immunomodulation on tumor immune microenvironment in acquired targeted therapy resistance and implication for immunotherapy resistance.Translational oncology · 2025Review
- OX-40 signaling promotes tumorigenesis in CTCL by regulating ERK activation.Frontiers in immunology · 2025Article
- Intermittent MEK Inhibition with GITR Costimulation Rescues T-cell Function for Increased Efficacy with CTLA-4 Blockade in Solid Tumor Models.Cancer immunology research · 2024Article
- Pericyte phenotype switching alleviates immunosuppression and sensitizes vascularized tumors to immunotherapy in preclinical models.The Journal of clinical investigation · 2024Article
- Beyond Anti-PD-1/PD-L1: Improving Immune Checkpoint Inhibitor Responses in Triple-Negative Breast Cancer.Cancers · 2024Review
- Activation of endogenous retroviruses and induction of viral mimicry by MEK1/2 inhibition in pancreatic cancer.Science advances · 2024Article
- Immunotherapy for the treatment of biliary tract cancer: an evolving landscape.Therapeutic advances in medical oncology · 2024Review
- Combined PARP and WEE1 inhibition triggers anti-tumor immune response in BRCA1/2 wildtype triple-negative breast cancer.NPJ breast cancer · 2023Article
24 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
18 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The presence of tumor-infiltrating lymphocytes in triple-negative breast cancers is correlated with improved outcomes. Ras/MAPK pathway activation is associated with significantly lower levels of tumor-infiltrating lymphocytes in triple-negative breast cancers and while MEK inhibition can promote recruitment of tumor-infiltrating lymphocytes to the tumor, here we show that MEK inhibition adversely affects early onset T-cell effector function. We show that α-4-1BB and α-OX-40 T-cell agonist antibodies can rescue the adverse effects of MEK inhibition on T cells in both mouse and human T cells, which results in augmented anti-tumor effects in vivo. This effect is dependent upon increased downstream p38/JNK pathway activation. Taken together, our data suggest that although Ras/MAPK pathway inhibition can increase tumor immunogenicity, the negative impact on T-cell activity is functionally important. This undesirable impact is effectively prevented by combination with T-cell immune agonist immunotherapies resulting in superior therapeutic efficacy.MEK inhibition in breast cancer is associated with increased tumour infiltrating lymphocytes (TILs), however, MAPK activity is required for T cells function. Here the authors show that TILs activity following MEK inhibition can be enhanced by agonist immunotherapy resulting in synergic therapeutic effects.
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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.