ArticleCancer immunology research2015
Type I cytokines synergize with oncogene inhibition to induce tumor growth arrest.
Article in Cancer immunology research, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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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
17 citing papers in PubMed, 27 citations in OpenAlex.
- Review
- Mechanisms of immune activation and regulation: lessons from melanoma.Nature reviews. Cancer · 2022Review
- Paradox breaker BRAF inhibitors have comparable potency and MAPK pathway reactivation to encorafenib in BRAF mutant colorectal cancer.Oncotarget · 2020Article
- Clinical cancer research : an official journal of the American Association for Cancer Research · 2020Article
- Identification of Small Molecule Enhancers of Immunotherapy for Melanoma.Scientific reports · 2020Article
- Tumour-intrinsic resistance to immune checkpoint blockade.Nature reviews. Immunology · 2020Review
- Article
- Oncodriver inhibition and CD4Oncotarget · 2018Article
- Allogeneic Human Double Negative T Cells as a Novel Immunotherapy for Acute Myeloid Leukemia and Its Underlying Mechanisms.Clinical cancer research : an official journal of the American Association for Cancer Research · 2018Article
- Acquired IFNγ resistance impairs anti-tumor immunity and gives rise to T-cell-resistant melanoma lesions.Nature communications · 2017Article
- A Pilot Trial of the Combination of Vemurafenib with Adoptive Cell Therapy in Patients with Metastatic Melanoma.Clinical cancer research : an official journal of the American Association for Cancer Research · 2017Article
- Ionic immune suppression within the tumour microenvironment limits T cell effector function.Nature · 2016Article
- Co-inhibition of colony stimulating factor-1 receptor and BRAF oncogene in mouse models of BRAFOncoimmunology · 2016Article
- Combining targeted therapy with immunotherapy. Can 1+1 equal more than 2?Seminars in immunology · 2016Review
- Restoring Lost Anti-HER-2 Th1 Immunity in Breast Cancer: A Crucial Role for Th1 Cytokines in Therapy and Prevention.Frontiers in pharmacology · 2016Review
- Cish actively silences TCR signaling in CD8+ T cells to maintain tumor tolerance.The Journal of experimental medicine · 2015Article
- Rationale for a Multimodality Strategy to Enhance the Efficacy of Dendritic Cell-Based Cancer Immunotherapy.Frontiers in immunology · 2015Review
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Authors and funding
27 authors at 1 institution in 1 country.
Funding
Abstract
Both targeted inhibition of oncogenic driver mutations and immune-based therapies show efficacy in treatment of patients with metastatic cancer, but responses can be either short lived or incompletely effective. Oncogene inhibition can augment the efficacy of immune-based therapy, but mechanisms by which these two interventions might cooperate are incompletely resolved. Using a novel transplantable BRAF(V600E)-mutant murine melanoma model (SB-3123), we explored potential mechanisms of synergy between the selective BRAF(V600E) inhibitor vemurafenib and adoptive cell transfer (ACT)-based immunotherapy. We found that vemurafenib cooperated with ACT to delay melanoma progression without significantly affecting tumor infiltration or effector function of endogenous or adoptively transferred CD8(+) T cells, as previously observed. Instead, we found that the T-cell cytokines IFNγ and TNFα synergized with vemurafenib to induce cell-cycle arrest of tumor cells in vitro. This combinatorial effect was recapitulated in human melanoma-derived cell lines and was restricted to cancers bearing a BRAF(V600E) mutation. Molecular profiling of treated SB-3123 indicated that the provision of vemurafenib promoted the sensitization of SB-3123 to the antiproliferative effects of T-cell effector cytokines. The unexpected finding that immune cytokines synergize with oncogene inhibitors to induce growth arrest has major implications for understanding cancer biology at the intersection of oncogenic and immune signaling and provides a basis for design of combinatorial therapeutic approaches for patients with metastatic cancer.
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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.