ArticleNature medicine2013
Persistent antigen at vaccination sites induces tumor-specific CD8⁺ T cell sequestration, dysfunction and deletion.
Article in Nature medicine, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 279 papers, 2 of them syntheses that pooled it.
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
279 citing papers in PubMed, 2 syntheses or guidelines pooled it, 446 citations in OpenAlex.
- Efficacy of vaccination therapy in newly diagnosed and recurrent glioblastoma patients: a meta-analysis.BMC cancer · 2025Pooled it
- Controlling timing and location in vaccines.Advanced drug delivery reviews · 2020Pooled it
- Phase I/II clinical trial of a melanoma vaccine targeting shared non-mutated antigens and a shared mutated BRAF neoantigen with an agonistic CD40 antibody (CDX-1140) plus TLR3 agonist (poly-ICLC).Journal for immunotherapy of cancer · 2026Trial
- Phase I/II trial of a long peptide vaccine (LPV7) plus toll-like receptor (TLR) agonists with or without incomplete Freund's adjuvant (IFA) for resected high-risk melanoma.Journal for immunotherapy of cancer · 2021Trial
- Characterization and comparison of innate and adaptive immune responses at vaccine sites in melanoma vaccine clinical trials.Cancer immunology, immunotherapy : CII · 2021Trial
- Combining a Universal Telomerase Based Cancer Vaccine With Ipilimumab in Patients With Metastatic Melanoma - Five-Year Follow Up of a Phase I/IIa Trial.Frontiers in immunology · 2021Trial
- Trial to evaluate the immunogenicity and safety of a melanoma helper peptide vaccine plus incomplete Freund's adjuvant, cyclophosphamide, and polyICLC (Mel63).Journal for immunotherapy of cancer · 2021Trial
- Bempegaldesleukin selectively depletes intratumoral Tregs and potentiates T cell-mediated cancer therapy.Nature communications · 2020Trial
- Combined Vaccination with NY-ESO-1 Protein, Poly-ICLC, and Montanide Improves Humoral and Cellular Immune Responses in Patients with High-Risk Melanoma.Cancer immunology research · 2020Trial
- A multipeptide vaccine plus toll-like receptor agonists LPS or polyICLC in combination with incomplete Freund's adjuvant in melanoma patients.Journal for immunotherapy of cancer · 2019Trial
- Autologous tumor cell vaccination combined with systemic CpG-B and IFN-α promotes immune activation and induces clinical responses in patients with metastatic renal cell carcinoma: a phase II trial.Cancer immunology, immunotherapy : CII · 2019Trial
- Intratumoral interferon-gamma increases chemokine production but fails to increase T cell infiltration of human melanoma metastases.Cancer immunology, immunotherapy : CII · 2016Trial
- Intramuscular plasmid DNA electroporation sequesters neoantigen-specific CD8Molecular therapy. Oncology · 2026Article
- Review
- Comparison of the adjuvant effect of AS01, AS03 and alum on the immune response to GMP-grade H5N1 antigen in guinea pigs.Scientific reports · 2026Article
- pVACtools v6: A comprehensive suite for neoantigen prediction, visualization, and therapy design.ArXiv · 2026Article
- Programming the immunological properties of mRNA vaccines for cancer.Nature reviews. Immunology · 2026Review
- Computational design and immunoinformatics validation of a T cell multi-epitope vaccine targeting glioblastoma stem cells.Scientific reports · 2026Article
- Bright side of the dark genome: antigens for next-gen cancer vaccines.Journal for immunotherapy of cancer · 2026Review
- Recent research progress and clinical status of immunotherapy for colorectal cancer.Journal of advanced research · 2026Review
219 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
20 authors at 2 institutions in 1 country.
Funding
Abstract
To understand why cancer vaccine-induced T cells often do not eradicate tumors, we studied immune responses in mice vaccinated with gp100 melanoma peptide in incomplete Freund's adjuvant (peptide/IFA), which is commonly used in clinical cancer vaccine trials. Peptide/IFA vaccination primed tumor-specific CD8(+) T cells, which accumulated not in tumors but rather at the persisting, antigen-rich vaccination site. Once there, primed T cells became dysfunctional and underwent antigen-driven, interferon-γ (IFN-γ)- and Fas ligand (FasL)-mediated apoptosis, resulting in hyporesponsiveness to subsequent vaccination. Provision of CD40-specific antibody, Toll-like receptor 7 (TLR7) agonist and interleukin-2 (IL-2) reduced T cell apoptosis but did not prevent vaccination-site sequestration. A nonpersisting vaccine formulation shifted T cell localization toward tumors, inducing superior antitumor activity while reducing systemic T cell dysfunction and promoting memory formation. These data show that persisting vaccine depots can induce specific T cell sequestration, dysfunction and deletion at vaccination sites; short-lived formulations may overcome these limitations and result in greater therapeutic efficacy of peptide-based cancer vaccines.
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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.