ArticleOncoimmunology2012
Selective BRAF inhibition decreases tumor-resident lymphocyte frequencies in a mouse model of human melanoma.
Article in Oncoimmunology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 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.
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
50 citing papers in PubMed, 79 citations in OpenAlex.
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- Encapsulation of soybean lunasin and amaranth unsaponifiable matter in liposomes induces cell cycle arrest in an allograft melanoma mouse model.Scientific reports · 2024Article
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- Global pannexin 1 deletion increases tumor-infiltrating lymphocytes in the BRAF/Pten mouse melanoma model.Molecular oncology · 2024Article
- Desmoplastic small round cell tumor: from genomics to targets, potential paths to future therapeutics.Frontiers in cell and developmental biology · 2024Review
- Combination of immune-checkpoint inhibitors and targeted therapies for melanoma therapy: The more, the better?Cancer metastasis reviews · 2023Review
- Sustained release hydrogel for durable locoregional chemoimmunotherapy for BRAF-mutated melanoma.Journal of controlled release : official journal of the Controlled Release Society · 2023Article
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- Development of Immunotherapy Combination Strategies in Cancer.Cancer discovery · 2021Review
- Spatiotemporal Analysis of B Cell- and Antibody Secreting Cell-Subsets in Human Melanoma Reveals Metastasis-, Tumor Stage-, and Age-Associated Dynamics.Frontiers in cell and developmental biology · 2021Article
- Dissecting the Lymphatic System to Predict Melanoma Metastasis.Frontiers in oncology · 2020Review
- Anti-OX40 Antibody Directly Enhances The Function of Tumor-Reactive CD8Clinical cancer research : an official journal of the American Association for Cancer Research · 2019Article
- B cells sustain inflammation and predict response to immune checkpoint blockade in human melanoma.Nature communications · 2019Article
- VIGLA-M: visual gene expression data analytics.BMC bioinformatics · 2019Article
- Strategies to Improve Cancer Immune Checkpoint Inhibitors Efficacy, Other Than Abscopal Effect: A Systematic Review.Cancers · 2019Review
- ΓJournal of oncology · 2019Review
- Article
- Oncogenic BRAFCancer research · 2018Article
- Structure-function analysis and therapeutic efficacy of antibodies to fungal melanin for melanoma radioimmunotherapy.Scientific reports · 2018Article
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 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The development of targeted therapies and immunotherapies has markedly advanced the treatment of metastasized melanoma. While treatment with selective BRAF(V600E) inhibitors (like vemurafenib or dabrafenib) leads to high response rates but short response duration, CTLA-4 blocking therapies induce sustained responses, but only in a limited number of patients. The combination of these diametric treatment approaches may further improve survival, but pre-clinical data concerning this approach is limited. We investigated, using Tyr::CreER(T2)PTEN(F-/-)BRAF(F-V600E/+) inducible melanoma mice, whether BRAF(V600E) inhibition can synergize with anti-CTLA-4 mAb treatment, focusing on the interaction between the BRAF(V600E) inhibitor PLX4720 and the immune system. While PLX4720 treatment strongly decreased tumor growth, it did not induce cell death in BRAF(V600E)/PTEN(-/-) melanomas. More strikingly, PLX4720 treatment led to a decreased frequency of tumor-resident T cells, NK-cells, MDSCs and macrophages, which could not be restored by the addition of anti-CTLA-4 mAb. As this effect was not observed upon treatment of BRAF wild-type B16F10 tumors, we conclude that the decreased frequency of immune cells correlates to BRAF(V600E) inhibition in tumor cells and is not due to an off-target effect of PLX4720 on immune cells. Furthermore, anti-CTLA-4 mAb treatment of inducible melanoma mice treated with PLX4720 did not result in enhanced tumor control, while anti-CTLA-4 mAb treatment did improve the effect of tumor-vaccination in B16F10-inoculated mice. Our data suggest that vemurafenib may negatively affect the immune activity within the tumor. Therefore, the potential effect of targeted therapy on the tumor-microenvironment should be taken into consideration in the design of clinical trials combining targeted and immunotherapy.
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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.