ArticleThe Journal of clinical investigation2013
Depleting tumor-specific Tregs at a single site eradicates disseminated tumors.
Article in The Journal of clinical investigation, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. It is linked to 3 registered trials, which are not on this map. Cited by 215 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Phase I-II Study of Intratumoral Urelumab Combined With Nivolumab in Patients With Solid Tumors
A Two-arm, Randomized, Non-comparative, Phase 2 Trial of AGEN2034 (Anti-PD-1) as a Monotherapy or Combination Therapy With AGEN1884 (Anti- CTLA4) or With Placebo in Women With Recurrent Cervical Cancer (Second Line) - RaPiDS
A Trial of Neoadjuvant, Hypofractionated Radiation, With Intratumoural Pembrolizumab Followed by Neoadjuvant Chemotherapy, in Stage 3 or High-risk Stage 2 Breast Cancer
Who cites it
215 citing papers in PubMed, 1 synthesis or guideline pooled it, 309 citations in OpenAlex.
- Identification and validation of TNFRSF4 as a high-profile biomarker for prognosis and immunomodulation in endometrial carcinoma.BMC cancer · 2022Pooled it
- Trial
- Trial
- Safety and activity of PD1 blockade by pidilizumab in combination with rituximab in patients with relapsed follicular lymphoma: a single group, open-label, phase 2 trial.The Lancet. Oncology · 2014Trial
- Targeting the Tumor Microenvironment Network to Overcome Immunotherapy Resistance in Non-Small Cell Lung Cancer: Mechanisms to Clinical Translation.Cancer medicine · 2026Review
- Peptidoglycan Suppresses Melanoma Growth in a Murine Model with Local Immune Activation.International journal of molecular sciences · 2026Article
- Intratumoral Regulatory T-cell Ablation Mediates Tumor Control Systemically without Autoimmunity.Cancer research · 2026Article
- First-in-human study of intravenous bispecific CTLA-4 × OX40 antibody (ATOR-1015) in advanced solid malignancies.ESMO open · 2026Article
- Timosaponin AIII enhances CAR-T cell potency and prevents relapse through impairing CAR-Tregs.Nature communications · 2026Article
- Prognostic immunological implications of OX40L expression in the tumor microenvironment of melanoma.Frontiers in immunology · 2026Article
- Non-α-biased IL-2 enhances both intratumoral and subcutaneous CpG/α-OX40 therapy, unleashing systemic antitumor immunity in mice.Journal for immunotherapy of cancer · 2025Article
- CD31 regulates metabolic switch in Treg migration attenuates rheumatoid arthritis.Clinical and translational medicine · 2025Article
- Methylated CpG ODNs fromInternational journal of molecular sciences · 2025Article
- HVJ-E links Apolipoprotein d to antitumor effects.Journal for immunotherapy of cancer · 2025Article
- Impact of tumor localization on antitumor immunity with conditionally activated CTLA-4 blockade.Journal for immunotherapy of cancer · 2025Article
- Phase I Trial to Evaluate the Safety of Intralesional Nivolumab Therapy for Limited Cutaneous Kaposi Sarcoma.JCO oncology advances · 2025Article
- Revealing the mechanisms and therapeutic potential of immune checkpoint proteins across diverse protein families.Frontiers in immunology · 2025Review
- Generation of novel human anti-OX-40 mAbs endowed with different biological properties as tools for cancer therapy.Frontiers in immunology · 2025Article
- Prospects for Treatment of Lung Cancer Using Activated Lymphocytes Combined with Other Anti-Cancer Modalities.Advances in respiratory medicine · 2024Review
- Spatial multiplex analysis of lung cancer reveals that regulatory T cells attenuate KRAS-G12C inhibitor-induced immune responses.Science advances · 2024Article
155 more citing papers are in PubMed but not listed here.
Corrections and comments
- Commented on by
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- Erratum issued
Authors and funding
16 authors at 4 institutions in 1 country.
Funding
Abstract
Activation of TLR9 by direct injection of unmethylated CpG nucleotides into a tumor can induce a therapeutic immune response; however, Tregs eventually inhibit the antitumor immune response and thereby limit the power of cancer immunotherapies. In tumor-bearing mice, we found that Tregs within the tumor preferentially express the cell surface markers CTLA-4 and OX40. We show that intratumoral coinjection of anti-CTLA-4 and anti-OX40 together with CpG depleted tumor-infiltrating Tregs. This in situ immunomodulation, which was performed with low doses of antibodies in a single tumor, generated a systemic antitumor immune response that eradicated disseminated disease in mice. Further, this treatment modality was effective against established CNS lymphoma with leptomeningeal metastases, sites that are usually considered to be tumor cell sanctuaries in the context of conventional systemic therapy. These results demonstrate that antitumor immune effectors elicited by local immunomodulation can eradicate tumor cells at distant sites. We propose that, rather than using mAbs to target cancer cells systemically, mAbs could be used to target the tumor infiltrative immune cells locally, thereby eliciting a systemic immune response.
Indexed as
Identifiers
What OpenQuestion holds
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.