ArticleJournal of hepatocellular carcinoma2021
The Combination Immunotherapy of TLR9 Agonist and OX40 Agonist via Intratumoural Injection for Hepatocellular Carcinoma.
Article in Journal of hepatocellular carcinoma, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 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
15 citing papers in PubMed, 20 citations in OpenAlex.
- Triplet RNA Lipid Nanoparticles for Locoregional Cancer Immunotherapy.Small science · 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
- Review
- A reliable prognostic model for hepatocellular carcinoma using neutrophil extracellular traps and immune related genes.Scientific reports · 2025Article
- Beyond Adaptive Immunity: Trained Innate Immune Responses as a Novel Frontier in Hepatocellular Carcinoma Therapy.Cancers · 2025Review
- SHR-1806, a robust OX40 agonist to promote T cell-mediated antitumor immunity.Cancer biology & therapy · 2024Article
- Overcoming Resistance to Immune Checkpoint Blockade in Liver Cancer with Combination Therapy: Stronger Together?Seminars in liver disease · 2024Review
- Design of a single-center, phase II trial to explore the efficacy and safety of 'R-ISV-RO' treatment in advanced tumors.Future oncology (London, England) · 2024Article
- Overcoming challenges in the delivery of STING agonists for cancer immunotherapy: A comprehensive review of strategies and future perspectives.Materials today. Bio · 2023Review
- Friend or Foe? Locoregional Therapies and Immunotherapies in the Current Hepatocellular Treatment Landscape.International journal of molecular sciences · 2023Review
- T cell-mediated targeted delivery of tadalafil regulates immunosuppression and polyamine metabolism to overcome immune checkpoint blockade resistance in hepatocellular carcinoma.Journal for immunotherapy of cancer · 2023Article
- Unleashing the efficacy of immune checkpoint inhibitors for advanced hepatocellular carcinoma: factors, strategies, and ongoing trials.Frontiers in pharmacology · 2023Review
- Combinatorial immunotherapies overcome MYC-driven immune evasion in triple negative breast cancer.Nature communications · 2022Article
- Immunologic Effects of Stereotactic Body Radiotherapy in Dogs with Spontaneous Tumors and the Impact of Intratumoral OX40/TLR Agonist Immunotherapy.International journal of molecular sciences · 2022Article
- Hydroxyapatite nanoparticles drive the potency of Toll-like receptor 9 agonist for amplified innate and adaptive immune response.Nano research · 2022Article
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThe response rate of immunotherapy via immune checkpoint blockade in hepatocellular carcinoma (HCC) is limited due to multiple immune evasion mechanisms. OX40 is a T cell co-stimulating molecule which suppresses the cancer immune evasion by activating effector T cells (Teffs) and counteracting regulatory T cells (Tregs). TLR9 belongs to the toll-like receptor superfamily which promotes tumour antigen presentation by stimulating the maturation of dendritic cells. Though the combination immunotherapy of TLR9 agonist (CpG) and OX40 agonist (anti-OX40 antibody) has shown encouraging efficacy in various tumours, its effect on HCC remains unknown. MATERIALS AND
methodsOrthotopic and ectopic HCC models were constructed by implanting Hepa1-6 cells at different body sites of the mice. Immune agents were administrated via three ways, including intratumoural injection into one site of the tumour, intraperitoneal injection, and subcutaneous injection. The anti-tumour immune response was evaluated by the regression of both the local treated tumour and distant untreated tumour. The ratio and function of CD4+ T cells, CD8+ T cells, Tregs and myeloid-derived suppressor cells (MDSCs) were analyzed by flow cytometry.
resultsCpG via intratumoural injection remarkably upregulated the weakly expressed OX40 of intratumoural T cells. The combination immunotherapy of CpG and anti-OX40 antibody via intratumoural injection significantly inhibited the growth of local and distant tumours, and also effectively prevented their recurrence. Excitingly, drug administration via intratumoural injection, rather than via intraperitoneal or subcutaneous injections, induced potent anti-tumour immune response. Furthermore, we demonstrated that the combination immunotherapy promoted CD8+ and CD4+ T cells, and inhibited Tregs and myeloid-derived suppressor cells, contributing to the effective inhibition on HCC. Noteworthily, the combination immunotherapy also induced an immune memory response.
conclusionThe intratumoural administration of combined CpG and anti-OX40 antibody serves as a promising immunotherapy against HCC.
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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.