ArticlePloS one2008
Treg depletion inhibits efficacy of cancer immunotherapy: implications for clinical trials.
Article in PloS one, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 72 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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
72 citing papers in PubMed, 134 citations in OpenAlex.
- Effect of Modified Vaccinia Ankara-5T4 and Low-Dose Cyclophosphamide on Antitumor Immunity in Metastatic Colorectal Cancer: A Randomized Clinical Trial.JAMA oncology · 2017Trial
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- Aging-Driven Immunosuppression: The Role of Tregs in the Ovarian Tumor Microenvironment.Aging cell · 2026Article
- AI-based pathomics model predicts regulatory T cell infiltration and radiotherapy response in IDH-wild-type glioblastoma.Frontiers in immunology · 2026Article
- Using major histocompatibility complex (MHC) II expression to predict antitumor response to CD4 + lymphocyte depletion.Scientific reports · 2025Article
- The need for paradigm shift: prognostic significance and implications of standard therapy-related systemic immunosuppression in glioblastoma for immunotherapy and oncolytic virotherapy.Frontiers in immunology · 2024Review
- Reprogramming the tumor microenvironment with biotechnology.Biomaterials research · 2023Review
- Protean role of epigenetic mechanisms and their impact in regulating the Tregs in TME.Cancer gene therapy · 2022Article
- Review
- Different syngeneic tumors show distinctive intrinsic tumor-immunity and mechanisms of actions (MOA) of anti-PD-1 treatment.Scientific reports · 2022Article
- Tissue Resident Foxp3Frontiers in immunology · 2022Review
- The immunosuppressive microenvironment and immunotherapy in human glioblastoma.Frontiers in immunology · 2022Review
- Genetic Alterations in Gliomas Remodel the Tumor Immune Microenvironment and Impact Immune-Mediated Therapies.Frontiers in oncology · 2021Review
- Dendritic Cell Vaccination of Glioblastoma: Road to Success or Dead End.Frontiers in immunology · 2021Review
- CD36-mediated metabolic adaptation supports regulatory T cell survival and function in tumors.Nature immunology · 2020Article
- T-Regulatory Cells In Tumor Progression And Therapy.Cancer management and research · 2019Review
- Review
- IL-33 Promotes the Development of Colorectal Cancer Through Inducing Tumor-Infiltrating ST2LTechnology in cancer research & treatment · 2018Article
- Targeting CD38 Suppresses Induction and Function of T Regulatory Cells to Mitigate Immunosuppression in Multiple Myeloma.Clinical cancer research : an official journal of the American Association for Cancer Research · 2017Article
12 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
8 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundRegulatory T lymphocytes (Treg) infiltrate human glioblastoma (GBM); are involved in tumor progression and correlate with tumor grade. Transient elimination of Tregs using CD25 depleting antibodies (PC61) has been found to mediate GBM regression in preclinical models of brain tumors. Clinical trials that combine Treg depletion with tumor vaccination are underway to determine whether transient Treg depletion can enhance anti-tumor immune responses and improve long term survival in cancer patients.
findingsUsing a syngeneic intracrabial glioblastoma (GBM) mouse model we show that systemic depletion of Tregs 15 days after tumor implantation using PC61 resulted in a decrease in Tregs present in tumors, draining lymph nodes and spleen and improved long-term survival (50% of mice survived >150 days). No improvement in survival was observed when Tregs were depleted 24 days after tumor implantation, suggesting that tumor burden is an important factor for determining efficacy of Treg depletion in clinical trials. In a T cell dependent model of brain tumor regression elicited by intratumoral delivery of adenoviral vectors (Ad) expressing Fms-like Tyrosine Kinase 3 ligand (Flt3L) and Herpes Simplex Type 1-Thymidine Kinase (TK) with ganciclovir (GCV), we demonstrate that administration of PC61 24 days after tumor implantation (7 days after treatment) inhibited T cell dependent tumor regression and long term survival. Further, depletion with PC61 completely inhibited clonal expansion of tumor antigen-specific T lymphocytes in response to the treatment.
conclusionsOur data demonstrate for the first time, that although Treg depletion inhibits the progression/eliminates GBM tumors, its efficacy is dependent on tumor burden. We conclude that this approach will be useful in a setting of minimal residual disease. Further, we also demonstrate that Treg depletion, using PC61 in combination with immunotherapy, inhibits clonal expansion of tumor antigen-specific T cells, suggesting that new, more specific targets to block Tregs will be necessary when used in combination with therapies that activate anti-tumor immunity.
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What OpenQuestion holds
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.