ArticleImmunity, inflammation and disease2017
Transient Treg depletion enhances therapeutic anti-cancer vaccination.
Article in Immunity, inflammation and disease, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed.
- CAR T cells targeting CCR4 selectively deplete human Tregs ex vivo and in vivo.Blood advances · 2026Article
- The Streptomyces Metabolite Thiostrepton Inhibits Regulatory T Cell Differentiation and Function to Boost Antitumor Immune Responses.European journal of immunology · 2025Article
- AMPK is necessary for Treg functional adaptation to microenvironmental stress during malignancy and viral pneumonia.The Journal of clinical investigation · 2025Article
- Regulatory T cells in solid tumor immunotherapy: effect, mechanism and clinical application.Cell death & disease · 2025Review
- The Trojan Horse Within: Mechanisms of Immune Evasion in Breast Cancer.Cancer heterogeneity and plasticity · 2025Article
- Peripheral-derived regulatory T cells contribute to tumor-mediated immune suppression in a nonredundant manner.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- The immunosuppressive landscape in tumor microenvironment.Immunologic research · 2024Review
- VEGFR affects miR-3200-3p-mediated regulatory T cell senescence in tumour-derived exosomes in non-small cell lung cancer.Functional & integrative genomics · 2024Article
- A telomere-targeting drug depletes cancer initiating cells and promotes anti-tumor immunity in small cell lung cancer.Nature communications · 2024Article
- Targeting the activin receptor 1C on CD4+ T cells for cancer immunotherapy.Oncoimmunology · 2024Article
- AMP-activated protein kinase is necessary for Treg cell functional adaptation to microenvironmental stress.bioRxiv : the preprint server for biology · 2023Article
- Both intratumoral regulatory T cell depletion and CTLA-4 antagonism are required for maximum efficacy of anti-CTLA-4 antibodies.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Identifying highly active anti-CCR4 CAR T cells for the treatment of T-cell lymphoma.Blood advances · 2023Article
- A Specific CD44lo CD25lo Subpopulation of Regulatory T Cells Inhibits Anti-Leukemic Immune Response and Promotes the Progression in a Mouse Model of Chronic Lymphocytic Leukemia.Frontiers in immunology · 2022Article
- Metabolic profiles of regulatory T cells in the tumour microenvironment.Cancer immunology, immunotherapy : CII · 2021Review
- Single-Cell Sequencing Reveals the Transcriptome and TCR Characteristics of pTregs andFrontiers in immunology · 2021Article
- Pushing Past the Blockade: Advancements in T Cell-Based Cancer Immunotherapies.Frontiers in immunology · 2021Review
- Biological Factors behind Melanoma Response to Immune Checkpoint Inhibitors.International journal of molecular sciences · 2020Review
- The multifaceted Foxp3European journal of immunology · 2020Article
- Pre-treatment tumor neo-antigen responses in draining lymph nodes are infrequent but predict checkpoint blockade therapy outcome.Oncoimmunology · 2020Article
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Authors and funding
14 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
introductionRegulatory T cells (Treg) play an important role in suppressing anti- immunity and their depletion has been linked to improved outcomes. To better understand the role of Treg in limiting the efficacy of anti-cancer immunity, we used a Diphtheria toxin (DTX) transgenic mouse model to specifically target and deplete Treg.
methodsTumor bearing BALB/c FoxP3.dtr transgenic mice were subjected to different treatment protocols, with or without Treg depletion and tumor growth and survival monitored.
resultsDTX specifically depleted Treg in a transient, dose-dependent manner. Treg depletion correlated with delayed tumor growth, increased effector T cell (Teff) activation, and enhanced survival in a range of solid tumors. Tumor regression was dependent on Teffs as depletion of both CD4 and CD8 T cells completely abrogated any survival benefit. Severe morbidity following Treg depletion was only observed, when consecutive doses of DTX were given during peak CD8 T cell activation, demonstrating that Treg can be depleted on multiple occasions, but only when CD8 T cell activation has returned to base line levels. Finally, we show that even minimal Treg depletion is sufficient to significantly improve the efficacy of tumor-peptide vaccination.
conclusionsBALB/c.FoxP3.dtr mice are an ideal model to investigate the full therapeutic potential of Treg depletion to boost anti-tumor immunity. DTX-mediated Treg depletion is transient, dose-dependent, and leads to strong anti-tumor immunity and complete tumor regression at high doses, while enhancing the efficacy of tumor-specific vaccination at low doses. Together this data highlight the importance of Treg manipulation as a useful strategy for enhancing current and future cancer immunotherapies.
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