ArticleThe Journal of clinical investigation2023
Linked CD4+/CD8+ T cell neoantigen vaccination overcomes immune checkpoint blockade resistance and enables tumor regression.
Article in The Journal of clinical investigation, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 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.
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Who cites it
46 citing papers in PubMed, 57 citations in OpenAlex.
- Therapeutic vaccines targeting solid tumors: A series of clinical trial analysis over the past decade.Translational oncology · 2026Review
- The Central Role of HLA Class II-Restricted Helper Neoantigen Vaccines in Cancer Immunotherapy.Cancers · 2026Review
- Decoding neoantigen-encoding tumor-specific transcripts unveils a shared target reservoir for immunotherapy in hepatocellular carcinoma.Journal for immunotherapy of cancer · 2026Article
- OT-55 reshapes tolerogenic BH3-mimetic-induced apoptosis toward immunogenic cell death in acute myeloid leukemia, potentiating PD-1/Tim-3 blockade.Cell death & disease · 2026Article
- An integrated analysis of MEN1 reveals its associations with clinical outcomes, cellular pathways, and the immune microenvironment.World journal of surgical oncology · 2026Article
- Multiomics prediction and immunogenic validation of personalized neoantigens in cholangiocarcinoma patients.Journal of translational medicine · 2026Article
- PMGen: from peptide-MHC structure prediction to peptide generation.Bioinformatics (Oxford, England) · 2026Article
- Vaccination with cationic liposome-encapsulated CD4 and CD8 T cell neoepitopes induces superior tumor control.Materials today. Bio · 2026Article
- Neoantigen Targeting as a Novel Approach for Therapy-Resistant Tumors.Molecular diagnosis & therapy · 2026Review
- CD4Cancer biology & medicine · 2026Review
- Dynamic changes in peripheral blood lymphocyte subsets predict the efficacy and prognosis of immune checkpoint inhibitors in metastatic osteosarcoma.Frontiers in immunology · 2026Article
- Enhancing cancer vaccine efficacy via electrostatic engineering of an FcγR-targeted protein.Frontiers in immunology · 2026Article
- New inflammatory markers associated with disease activity in patients with antineutrophil cytoplasmic Antibody-associated vasculitis.Clinical and experimental medicine · 2025Article
- Structural changes from wild-type define tumor-rejecting neoantigens.Journal for immunotherapy of cancer · 2025Article
- Biomimetic nanovaccines in cancer therapy: mechanisms, efficacy, and clinical translation.Materials today. Bio · 2025Review
- Neo-antigen tumor vaccination depends on CD4-licensing conveyed by adeno-associated virus like particles.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- Addressing clinical needs in NSCLC immunotherapy: Mechanisms of resistance and promising combination strategies.Cell reports. Medicine · 2025Review
- The spontaneous neoantigen-specific CD4Journal for immunotherapy of cancer · 2025Article
- Nodal Expansion, Tumor Infiltration and Exhaustion of Neoepitope-Specific Th Cells After Prophylactic Peptide Vaccination and Anti-CTLA4 Therapy in Mouse Melanoma B16.International journal of molecular sciences · 2025Article
- Recent advances in therapeutic cancer vaccines.Nature reviews. Cancer · 2025Review
Corrections and comments
- Update ofLinked CD42023
Authors and funding
13 authors at 3 institutions in 2 countries.
Funding
Abstract
Therapeutic benefit to immune checkpoint blockade (ICB) is currently limited to the subset of cancers thought to possess a sufficient tumor mutational burden (TMB) to allow for the spontaneous recognition of neoantigens (NeoAg) by autologous T cells. We explored whether the response to ICB of an aggressive low-TMB squamous cell tumor could be improved through combination immunotherapy using functionally defined NeoAg as targets for endogenous CD4+ and CD8+ T cells. We found that, whereas vaccination with CD4+ or CD8+ NeoAg alone did not offer prophylactic or therapeutic immunity, vaccines containing NeoAg recognized by both subsets overcame ICB resistance and led to the eradication of large established tumors that contained a subset of PD-L1+ tumor-initiating cancer stem cells (tCSC), provided the relevant epitopes were physically linked. Therapeutic CD4+/CD8+ T cell NeoAg vaccination produced a modified tumor microenvironment (TME) with increased numbers of NeoAg-specific CD8+ T cells existing in progenitor and intermediate exhausted states enabled by combination ICB-mediated intermolecular epitope spreading. We believe that the concepts explored herein should be exploited for the development of more potent personalized cancer vaccines that can expand the range of tumors treatable with ICB.
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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.