ArticleJournal for immunotherapy of cancer2022
CD4 T cell dynamics shape the immune response to combination oncolytic herpes virus and BRAF inhibitor therapy for melanoma.
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 10 papers.
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Who cites it
10 citing papers in PubMed, 14 citations in OpenAlex.
- Review
- Comprehensive Analysis Based on the Cancer-Immunity Cycle Identifies a Novel Immunosuppressive Subtype of Bladder Cancer.International journal of genomics · 2026Article
- Oncolytic Herpes Simplex Virus Therapy: Latest Advances, Core Challenges, and Future Outlook.Vaccines · 2025Review
- TockyPrep: data preprocessing methods for flow cytometric fluorescent timer analysis.BMC bioinformatics · 2025Article
- TockyLocus: quantitative analysis of flow cytometric fluorescent timer data in Nr4a3-Tocky and Foxp3-Tocky mice.Biology methods & protocols · 2025Article
- Immunological Considerations for the Development of an Effective Herpes Vaccine.Microorganisms · 2024Review
- Sculpting the tumour microenvironment by combining radiotherapy and ATR inhibition for curative-intent adjuvant immunotherapy.Nature communications · 2024Article
- Combination of oncolytic Maraba virus with immune checkpoint blockade overcomes therapy resistance in an immunologically cold model of advanced melanoma with dysfunctional T-cell receptor signalling.Journal for immunotherapy of cancer · 2024Article
- Elucidating molecular and cellular mechanisms of singularity phenomena in immunology.Biophysics and physicobiology · 2024Article
- HSV: The scout and assault for digestive system tumors.Frontiers in molecular biosciences · 2023Review
Corrections and comments
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Authors and funding
22 authors at 5 institutions in 2 countries.
Funding
Abstract
backgroundCombination herpes simplex virus (HSV) oncolytic virotherapy and BRAF inhibitors (BRAFi) represent promising immunogenic treatments for BRAF mutant melanoma, but an improved understanding of the immunobiology of combinations is needed to improve on the benefit of immune checkpoint inhibitors (ICI).
methodsUsing a BRAF
resultsAdding BRAFi treatment to HSV improved anti-tumor effects in vivo but not in vitro. Immune characterization showed HSV or dual therapy led to fewer intratumoral Treg, although with a more activated phenotype, together with more effector CD8 +T cells. Tocky analysis further showed that HSV/BRAFi dual treatment reduced the Tocky signal (reflecting engagement with cognate antigen), in both Treg and conventional subsets of CD4+, but not in CD8 +cells. However, a higher percentage of Treg than of conventional CD4 +maintained frequent engagement with antigens on treatment, reflecting a predominance of suppressive over effector function within the CD4 +compartment. The only T cell subset which correlated with a reduction in tumor growth was within Tocky signal positive conventional CD4+, supporting their therapeutic role. Targeting CD25 high, antigen-engaged Treg with a depleting anti-CD25 ICI, achieved complete cures in 100% of mice with triple therapy. Transcriptomic analysis confirmed reduction in Foxp3 on addition of anti-CD25 to HSV/BRAFi, as well as increases in expression of genes reflecting interferon signaling and cytotoxic activity.
conclusionsCombination HSV/BRAFi is an immunogenic therapy for BRAF mutant melanoma, but cannot fully control tumors. Dual therapy results in changes in T cell dynamics within tumors, with relatively maintained antigen signaling in Treg compared with conv CD4+. Antigen-engaged CD4 +effectors correlate with tumor growth control, and depletion of Treg by addition of an anti-CD25 ICI, releasing suppression of conventional CD4 +effectors by Treg, enhances survival and activates immune signaling within tumors.
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