ArticleCancer immunology research2014
Apoptosis-regulated low-avidity cancer-specific CD8(+) T cells can be rescued to eliminate HER2/neu-expressing tumors by costimulatory agonists in tolerized mice.
Article in Cancer immunology research, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
What it found
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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.
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Who cites it
18 citing papers in PubMed, 21 citations in OpenAlex.
- Mutant KRAS vaccine with dual checkpoint blockade in resected pancreatic cancer: a phase I trial.Nature communications · 2026Article
- The diversity of CD8Nature reviews. Immunology · 2025Review
- Biological and clinical significance of tumour-infiltrating lymphocytes in the era of immunotherapy: a multidimensional approach.Nature reviews. Clinical oncology · 2025Review
- Kidney Cancer and Chronic Kidney Disease: Too Close for Comfort.Biomedicines · 2021Review
- Mechanisms that allow vaccination against an oncolytic vesicular stomatitis virus-encoded transgene to enhance safety without abrogating oncolysis.Scientific reports · 2021Article
- Safety and Efficacy of Personalized Cancer Vaccines in Combination With Immune Checkpoint Inhibitors in Cancer Treatment.Frontiers in oncology · 2021Review
- Robust antigen-specific CD8 T cell tolerance to a model prostate cancer neoantigen.Oncoimmunology · 2020Article
- The pursuit of transplantation tolerance: new mechanistic insights.Cellular & molecular immunology · 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
- Combining STING-based neoantigen-targeted vaccine with checkpoint modulators enhances antitumor immunity in murine pancreatic cancer.JCI insight · 2018Article
- Distinct Graft-Specific TCR Avidity Profiles during Acute Rejection and Tolerance.Cell reports · 2018Article
- Emerging strategies for combination checkpoint modulators in cancer immunotherapy.The Journal of clinical investigation · 2018Review
- Dual Inhibition of Hedgehog and c-Met Pathways for Pancreatic Cancer Treatment.Molecular cancer therapeutics · 2017Article
- AJournal of immunology (Baltimore, Md. : 1950) · 2017Article
- A STING Agonist Given with OX40 Receptor and PD-L1 Modulators Primes Immunity and Reduces Tumor Growth in Tolerized Mice.Cancer immunology research · 2017Article
- Low Antigen Dose in Adjuvant-Based Vaccination Selectively Induces CD4 T Cells with Enhanced Functional Avidity and Protective Efficacy.Journal of immunology (Baltimore, Md. : 1950) · 2017Article
- Survivin-targeted immunotherapy drives robust polyfunctional T cell generation and differentiation in advanced ovarian cancer patients.Oncoimmunology · 2015Article
- Identifying Individual T Cell Receptors of Optimal Avidity for Tumor Antigens.Frontiers in immunology · 2015Review
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
A major barrier to vaccines in cancer treatment is their failure to activate and maintain a complete cancer-specific CD8(+) effector T-cell repertoire. Low-avidity T cells are more likely to escape clonal deletion in the thymus when compared with high-avidity T cells, and therefore comprise the major population of effector T cells available for activation in patients with cancer. However, low-avidity T cells fail to traffic into the tumor microenvironment and function in eradicating tumor under optimal vaccination conditions as opposed to high-avidity T cells that escape clonal deletion and function in tumor killing. We used high- and low-avidity T-cell receptor transgenic CD8(+) T cells specific for the immunodominant epitope HER2/neu (RNEU420-429) to identify signaling pathways responsible for the inferior activity of the low-avidity T cells. Adoptive transfer of these cells into tumor-bearing vaccinated mice identified the members of apoptosis pathways that are upregulated in low-avidity T cells. The increased expression of proapoptotic proteins by low-avidity T cells promoted their own cell death and also that of other tumor-specific CD8(+) T cells within their local environment. Importantly, we show that this proapoptotic effect can be overcome by using a strong costimulatory signal that prevents the activation-induced cell death and enables the low-avidity T cells to traffic into the tumor and assist in tumor clearance. These findings identify new therapeutic opportunities for activating the most potent anticancer T-cell responses.
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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.