ArticlePloS one2012
Trafficking of high avidity HER-2/neu-specific T cells into HER-2/neu-expressing tumors after depletion of effector/memory-like regulatory T cells.
Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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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
28 citing papers in PubMed, 44 citations in OpenAlex.
- A feasibility study of cyclophosphamide, trastuzumab, and an allogeneic GM-CSF-secreting breast tumor vaccine for HER2+ metastatic breast cancer.Cancer immunology research · 2014Trial
- Immunotherapy converts nonimmunogenic pancreatic tumors into immunogenic foci of immune regulation.Cancer immunology research · 2014Trial
- Effects of cyclophosphamide and IL-2 on regulatory CD4+ T cell frequency and function in melanoma patients vaccinated with HLA-class I peptides: impact on the antigen-specific T cell response.Cancer immunology, immunotherapy : CII · 2013Trial
- Host-derived interleukin-1α drives tumor immunosuppression by reprogramming tumor-associated myeloid cells.NPJ breast cancer · 2026Article
- Biological and clinical significance of tumour-infiltrating lymphocytes in the era of immunotherapy: a multidimensional approach.Nature reviews. Clinical oncology · 2025Review
- Robust antigen-specific CD8 T cell tolerance to a model prostate cancer neoantigen.Oncoimmunology · 2020Article
- T-cell receptor affinity in the age of cancer immunotherapy.Molecular carcinogenesis · 2020Review
- Immune-Checkpoint Blockade Opposes CD8Cancer immunology research · 2019Article
- A CD40 Agonist and PD-1 Antagonist Antibody Reprogram the Microenvironment of Nonimmunogenic Tumors to Allow T-cell-Mediated Anticancer Activity.Cancer immunology research · 2019Article
- Entinostat Converts Immune-Resistant Breast and Pancreatic Cancers into Checkpoint-Responsive Tumors by Reprogramming Tumor-Infiltrating MDSCs.Cancer immunology research · 2018Article
- Article
- A STING Agonist Given with OX40 Receptor and PD-L1 Modulators Primes Immunity and Reduces Tumor Growth in Tolerized Mice.Cancer immunology research · 2017Article
- Sorafenib combined with HER-2 targeted vaccination can promote effective T cell immunity in vivo.International immunopharmacology · 2017Article
- Definitive activation of endogenous antitumor immunity by repetitive cycles of cyclophosphamide with interspersed Toll-like receptor agonists.Oncotarget · 2016Article
- Aberrant Glycosylation of Anchor-Optimized MUC1 Peptides Can Enhance Antigen Binding Affinity and Reverse Tolerance to Cytotoxic T Lymphocytes.Biomolecules · 2016Article
- Galectin-3 Shapes Antitumor Immune Responses by Suppressing CD8+ T Cells via LAG-3 and Inhibiting Expansion of Plasmacytoid Dendritic Cells.Cancer immunology research · 2015Article
- Control of CD8 T-Cell Infiltration into Tumors by Vasculature and Microenvironment.Advances in cancer research · 2015Review
- Identifying Individual T Cell Receptors of Optimal Avidity for Tumor Antigens.Frontiers in immunology · 2015Review
- Enhancement of T cell recruitment and infiltration into tumours.Clinical and experimental immunology · 2014Review
- T cell avidity and tumor immunity: problems and solutions.Cancer microenvironment : official journal of the International Cancer Microenvironment Society · 2014Article
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
backgroundCancer vaccines are designed to activate and enhance cancer-antigen-targeted T cells that are suppressed through multiple mechanisms of immune tolerance in cancer-bearing hosts. T regulatory cell (Treg) suppression of tumor-specific T cells is one barrier to effective immunization. A second mechanism is the deletion of high avidity tumor-specific T cells, which leaves a less effective low avidity tumor specific T cell repertoire available for activation by vaccines. Treg depleting agents including low dose cyclophosphamide (Cy) and antibodies that deplete CD25-expressing Tregs have been used with limited success to enhance the potency of tumor-specific vaccines. In addition, few studies have evaluated mechanisms that activate low avidity cancer antigen-specific T cells. Therefore, we developed high and low avidity HER-2/neu-specific TCR transgenic mouse colonies specific for the same HER-2/neu epitope to define the tolerance mechanisms that specifically affect high versus low avidity tumor-specific T cells. METHODOLOGY/PRINCIPAL
findingsHigh and low avidity CD8(+) T cell receptor (TCR) transgenic mice specific for the breast cancer antigen HER-2/neu (neu) were developed to provide a purified source of naïve, tumor-specific T cells that can be used to study tolerance mechanisms. Adoptive transfer studies into tolerant FVB/N-derived HER-2/neu transgenic (neu-N) mice demonstrated that high avidity, but not low avidity, neu-specific T cells are inhibited by Tregs as the dominant tolerizing mechanism. High avidity T cells persisted, produced IFNγ, trafficked into tumors, and lysed tumors after adoptive transfer into mice treated with a neu-specific vaccine and low dose Cy to deplete Tregs. Analysis of Treg subsets revealed a Cy-sensitive CD4(+)Foxp3(+)CD25(low) tumor-seeking migratory phenotype, characteristic of effector/memory Tregs, and capable of high avidity T cell suppression. CONCLUSION/SIGNIFICANCE: Depletion of CD25(low) Tregs allows activation of tumor-clearing high avidity T cells. Thus, the development of agents that specifically deplete Treg subsets should translate into more effective immunotherapies while avoiding autoimmunity.
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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.