ArticleCancer research2013
High-avidity T cells are preferentially tolerized in the tumor microenvironment.
Article in Cancer research, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It has been retracted, and should not be counted. Cited by 26 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.
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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
26 citing papers in PubMed, 35 citations in OpenAlex.
- A replicating LCMV-based vaccine for the treatment of solid tumors.Molecular therapy : the journal of the American Society of Gene Therapy · 2024Article
- Vaccination with post-translational modified, homocitrullinated peptides induces CD8 T-cell responses that mediate antitumor immunity.Journal for immunotherapy of cancer · 2023Article
- Protective low-avidity anti-tumour CD8+ T cells are selectively attenuated by regulatory T cells.Immunotherapy advances · 2021Article
- Novel progresses of chimeric antigen receptor (CAR) T cell therapy in multiple myeloma.Stem cell investigation · 2021Review
- Vaccination with High-Affinity Epitopes Impairs Antitumor Efficacy by Increasing PD-1 Expression on CD8Cancer immunology research · 2017Article
- 5T4 oncofoetal glycoprotein: an old target for a novel prostate cancer immunotherapy.Oncotarget · 2017Article
- Article
- SCIB1, a huIgG1 antibody DNA vaccination, combined with PD-1 blockade induced efficient therapy of poorly immunogenic tumors.Oncotarget · 2016Article
- T Cell Cancer Therapy Requires CD40-CD40L Activation of Tumor Necrosis Factor and Inducible Nitric-Oxide-Synthase-Producing Dendritic Cells.Cancer cell · 2016Article
- SCIB2, an antibody DNA vaccine encoding NY-ESO-1 epitopes, induces potent antitumor immunity which is further enhanced by checkpoint blockade.Oncoimmunology · 2016Article
- Purinergic regulation of the immune system.Nature reviews. Immunology · 2016Review
- FOXO3-NF-κB RelA Protein Complexes Reduce Proinflammatory Cell Signaling and Function.Journal of immunology (Baltimore, Md. : 1950) · 2015Article
- CD4+ T Cell Help Selectively Enhances High-Avidity Tumor Antigen-Specific CD8+ T Cells.Journal of immunology (Baltimore, Md. : 1950) · 2015Article
- Immune Regulation by Self-Recognition: Novel Possibilities for Anticancer Immunotherapy.Journal of the National Cancer Institute · 2015Article
- Genetic vaccines to potentiate the effective CD103+ dendritic cell-mediated cross-priming of antitumor immunity.Journal of immunology (Baltimore, Md. : 1950) · 2015Article
- Identifying Individual T Cell Receptors of Optimal Avidity for Tumor Antigens.Frontiers in immunology · 2015Review
- Transforming growth factor β-mediated suppression of antitumor T cells requires FoxP1 transcription factor expression.Immunity · 2014Article
- T cell avidity and tumor immunity: problems and solutions.Cancer microenvironment : official journal of the International Cancer Microenvironment Society · 2014Article
- Elimination of IL-10-inducing T-helper epitopes from an IGFBP-2 vaccine ensures potent antitumor activity.Cancer research · 2014Article
- Apoptosis-regulated low-avidity cancer-specific CD8(+) T cells can be rescued to eliminate HER2/neu-expressing tumors by costimulatory agonists in tolerized mice.Cancer immunology research · 2014Article
Corrections and comments
- Retraction · 2016-03-24Falsification/Fabrication of Data · Investigation by ORI · Misconduct - Official Investigation(s) and/or Finding(s) · Misconduct by Author · · Misconduct by Stephanie Watkins;
- Retracted
Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
Abstract
One obstacle in eliciting potent antitumor immune responses is the induction of tolerance to tumor antigens. TCR(lo) mice bearing a TCR transgene specific for the melanoma antigen tyrosinase-related protein-2 (TRP-2, Dct) harbor T cells that maintain tumor antigen responsiveness but lack the ability to control melanoma outgrowth. We used this model to determine whether higher avidity T cells could control tumor growth without becoming tolerized. As a part of the current study, we developed a second TRP-2-specific TCR transgenic mouse line (TCR(hi)) that bears higher avidity T cells and spontaneously developed autoimmune depigmentation. In contrast to TCR(lo) T cells, which were ignorant of tumor-derived antigen, TCR(hi) T cells initially delayed subcutaneous B16 melanoma tumor growth. However, persistence in the tumor microenvironment resulted in reduced IFN-γ production and CD107a (Lamp1) mobilization, hallmarks of T-cell tolerization. IFN-γ expression by TCR(hi) T cells was critical for upregulation of MHC-I on tumor cells and control of tumor growth. Blockade of PD-1 signals prevented T-cell tolerization and restored tumor immunity. Depletion of tumor-associated dendritic cells (TADC) reduced tolerization of TCR(hi) T cells and enhanced their antitumor activity. In addition, TADCs tolerized TCR(hi) T cells but not TCR(lo) T cells in vitro. Our findings show that T-cell avidity is a critical determinant of not only tumor control but also susceptibility to tolerization in the tumor microenvironment. For this reason, care should be exercised when considering T-cell avidity in designing cancer immunotherapeutics.
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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.