ArticleThe Journal of clinical investigation2019
In situ vaccination with defined factors overcomes T cell exhaustion in distant tumors.
Article in The Journal of clinical investigation, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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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
35 citing papers in PubMed.
- Review
- T Cell Exhaustion in Cancer Immunotherapy: Heterogeneity, Mechanisms, and Therapeutic Opportunities.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- IL10R Inhibition Induces Neutrophil Tumoricidal Activity.Cancer immunology research · 2026Article
- Immunogenic tumor cell death and T-cell-derived IFN-γ elicit tumoricidal macrophages to potentiate OX40 immunotherapy.Cell reports. Medicine · 2026Article
- Vaccination rescues dysfunctional T cell therapy by amplifying rare stem-like antitumor CD8Research square · 2026Article
- Agonistic CD40 elicits CD8+ T-cell-dependent primary responses and CD4+ T-cell-dependent long-term immunity in breast cancer.NPJ breast cancer · 2026Article
- Interferon Epsilon Loss Is Elusive 9p21 Link to Immune-Cold Tumors, Resistant to Immune Checkpoint Therapy, and Endogenous CXCL9/10 Induction.Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer · 2025Review
- VAX014 Activates Tumor-Intrinsic STING and RIG-I to Promote the Development of Antitumor Immunity.Molecular cancer therapeutics · 2025Article
- Redefining bladder cancer treatment: innovations in overcoming drug resistance and immune evasion.Frontiers in immunology · 2025Review
- Current and future immunotherapeutic approaches in pancreatic cancer treatment.Journal of hematology & oncology · 2024Review
- APR-246 increases tumor antigenicity independent of p53.Life science alliance · 2024Article
- Intralesional administration of VAX014 facilitates in situ immunization and potentiates immune checkpoint blockade in immunologically cold tumors.Journal for immunotherapy of cancer · 2023Article
- Genomic and immune landscape Of metastatic pheochromocytoma and paraganglioma.Nature communications · 2023Article
- In situ vaccination with cowpea mosaic virus elicits systemic antitumor immunity and potentiates immune checkpoint blockade.Journal for immunotherapy of cancer · 2022Article
- Increased p53 expression induced by APR-246 reprograms tumor-associated macrophages to augment immune checkpoint blockade.The Journal of clinical investigation · 2022Article
- A decade of checkpoint blockade immunotherapy in melanoma: understanding the molecular basis for immune sensitivity and resistance.Nature immunology · 2022Review
- Innate Immunity and Cancer Pathophysiology.Annual review of pathology · 2022Review
- Enhancing immunotherapy in cancer by targeting emerging immunomodulatory pathways.Nature reviews. Clinical oncology · 2022Review
- CD40 and CD80/86 signaling in cDC1s mediate effective neoantigen vaccination and generation of antigen-specific CX3CR1Cancer immunology, immunotherapy : CII · 2022Article
- Influencing tumor-associated macrophages in malignant melanoma with monoclonal antibodies.Oncoimmunology · 2022Review
Corrections and comments
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Authors and funding
21 authors.
Funding
Abstract
Irreversible T cell exhaustion limits the efficacy of programmed cell death 1 (PD-1) blockade. We observed that dual CD40-TLR4 stimulation within a single tumor restored PD-1 sensitivity and that this regimen triggered a systemic tumor-specific CD8+ T cell response. This approach effectively treated established tumors in diverse syngeneic cancer models, and the systemic effect was dependent on the injected tumor, indicating that treated tumors were converted into necessary components of this therapy. Strikingly, this approach was associated with the absence of exhausted PD-1hi T cells in treated and distant tumors, while sparing the intervening draining lymph node and spleen. Furthermore, patients with transcription changes like those induced by this therapy experienced improved progression-free survival with anti-PD-1 treatment. Dual CD40-TLR4 activation within a single tumor is thus an approach for overcoming resistance to PD-1 blockade that is unique in its ability to cause the loss of exhausted T cells within tumors while sparing nonmalignant tissues.
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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.