ArticleCancer research2014
Immune-based antitumor effects of BRAF inhibitors rely on signaling by CD40L and IFNγ.
Article in Cancer research, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 85 papers.
What it found
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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.
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
85 citing papers in PubMed, 124 citations in OpenAlex.
- Sequential immunotherapy and targeted therapy for metastatic BRAF V600 mutated melanoma: 4-year survival and biomarkers evaluation from the phase II SECOMBIT trial.Nature communications · 2024Trial
- Regression-Associated Macrophages Recruit Natural Killer Cells That Constrain Targeted Therapy Resistance.Cancer research · 2026Article
- Integrated approaches to sensitizing melanoma to radiotherapy.Strahlentherapie und Onkologie : Organ der Deutschen Rontgengesellschaft ... [et al] · 2026Review
- CAR-T triggers TAM reeducation and adaptive anti-tumor response via TREM2 deficiency or CD40 agonist.Cell reports. Medicine · 2026Article
- CCL2/CCR2 signaling pathway in tumorigenesis and metastasis (Review).Oncology letters · 2025Review
- The tumour microenvironment in pancreatic cancer - new clinical challenges, but more opportunities.Nature reviews. Clinical oncology · 2025Review
- Article
- Immunomodulatory role of oncogenic alterations in non-small cell lung cancer: a review of implications for immunotherapy.Cancer metastasis reviews · 2025Review
- Advances in tumor-associated macrophage-mediated chemotherapeutic resistance in glioma.Frontiers in cell and developmental biology · 2025Review
- Tumor eradication by triplet therapy with BRAF inhibitor, TLR 7 agonist, and PD-1 antibody for BRAF-mutated melanoma.Cancer science · 2024Article
- Tumor-targeted therapy with BRAF-inhibitor recruits activated dendritic cells to promote tumor immunity in melanoma.Journal for immunotherapy of cancer · 2024Article
- Clinical Predictors of Survival in Patients With BRAFV600-Mutated Metastatic Melanoma Treated With Combined BRAF and MEK Inhibitors After Immune Checkpoint Inhibitors.The oncologist · 2024Article
- Immunomodulation of human T cells by microbubble-mediated focused ultrasound.Frontiers in immunology · 2024Article
- Combinatorial Immunotherapy with Agonistic CD40 Activates Dendritic Cells to Express IL12 and Overcomes PD-1 Resistance.Cancer immunology research · 2023Article
- Efficacy of Pembrolizumab in Advanced Melanoma: A Narrative Review.International journal of molecular sciences · 2023Review
- Engineered E. coli Nissle 1917 for delivery of bioactive IL-2 for cancer immunotherapy.Scientific reports · 2023Article
- Enhancing immunotherapy response in melanoma: myeloid-derived suppressor cells as a therapeutic target.The Journal of clinical investigation · 2023Review
- Combination of immune-checkpoint inhibitors and targeted therapies for melanoma therapy: The more, the better?Cancer metastasis reviews · 2023Review
- HIF: a master regulator of nutrient availability and metabolic cross-talk in the tumor microenvironment.The EMBO journal · 2023Review
- CD40 signal rewires fatty acid and glutamine metabolism for stimulating macrophage anti-tumorigenic functions.Nature immunology · 2023Article
25 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
6 authors at 2 institutions in 1 country.
Funding
Abstract
B-Raf(V600E) inhibitors have been suggested to promote tumor regression with the help of host immunity, but this hypothesis has not been examined directly in detail. In this study, we profiled immunologic changes in the tumor microenvironment and tumor-infiltrating lymphocytes (TIL) in a B-RafV600E/Pten-driven murine model of melanoma after administration of the B-Raf(V600E) small molecule inhibitor PLX4720. In this model, we found that as tumors developed, they gradually acquired immunosuppressive features, including accumulation of regulatory T cells (Treg) and CD11b(+)/Gr-1(+) myeloid cells and loss of Th1 effector functions on CD4(+) TILs, such as CD40L and IFNγ expression. PLX4720 administration promoted development of a more immune stimulatory microenvironment associated with a relative increase in CD40L and IFNγ expression on intratumoral CD4(+) TILs and a reduced accumulation of Tregs and CD11b(+)/Gr-1(+) myeloid cells. Strikingly, CD40L or IFNγ blockade compromised the ability of PLX4720 to inhibit melanoma growth. Supporting this result, agonistic CD40 antibody was sufficient to evoke antitumor immunity and suppress tumor growth in tumor-bearing mice. Taken together, our results establish the critical role of immune-related changes, with key contributions for CD40L and IFNγ signaling in the antitumor responses triggered in vivo by B-Raf(V600E) inhibitors.
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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.