ArticleCancers2022
Combination of OX40 Co-Stimulation, Radiotherapy, and PD-1 Inhibition in a Syngeneic Murine Triple-Negative Breast Cancer Model.
Article in Cancers, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 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
16 citing papers in PubMed, 24 citations in OpenAlex.
- Trial
- Radiotherapy and immunotherapy in cancer treatment: mechanisms of clinical synergy.The Journal of clinical investigation · 2026Review
- Simultaneous detection of lymphocytes and tumor cellsNanoscale horizons · 2026Article
- Beyond local control: radiotherapy-immunotherapy combinations fromFrontiers in genetics · 2026Review
- OX40 signaling in cancer immunotherapy: mechanisms of action, translational applications, and therapeutic perspectives.Frontiers in immunology · 2026Review
- Research progress in the construction and application of immunotherapy resistance models.Cancer immunology, immunotherapy : CII · 2025Review
- The untapped potential of radiation and immunotherapy for hormone receptor-positive breast cancer.NPJ breast cancer · 2025Review
- OX40-OX40L Axis in Cutaneous T-Cell Lymphomas: Pathogenic, Prognostic, and Potential Therapeutic Perspectives.Biomolecules · 2025Review
- Molecular mechanisms underlying the abscopal effect induced by radiotherapy and its synergistic translational potential with immunotherapy.Therapeutic advances in medical oncology · 2025Review
- OX40/OX40L: a new target for tumor immunotherapy and its clinical research progress.Frontiers in oncology · 2025Review
- The dynamic duo: A narrative review on the synergy between stereotactic body radiotherapy and immunotherapy in lung cancer treatment (Review).Oncology reports · 2024Review
- Molecular determinants of immunogenic cell death elicited by radiation therapy.Immunological reviews · 2024Review
- Modulation of CD8International journal of molecular sciences · 2023Review
- Radiation-induced tumor immune microenvironments and potential targets for combination therapy.Signal transduction and targeted therapy · 2023Review
- Molecular and functional imaging in cancer-targeted therapy: current applications and future directions.Signal transduction and targeted therapy · 2023Review
- Mechanistic rationales for combining immunotherapy with radiotherapy.Frontiers in immunology · 2023Review
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
Abstract
Immune checkpoint inhibitors have been successful in a wide range of tumor types but still have limited efficacy in immunologically cold tumors, such as breast cancers. We hypothesized that the combination of agonistic anti-OX40 (α-OX40) co-stimulation, PD-1 blockade, and radiotherapy would improve the therapeutic efficacy of the immune checkpoint blockade in a syngeneic murine triple-negative breast cancer model. Murine triple-negative breast cancer cells (4T1) were grown in immune-competent BALB/c mice, and tumors were irradiated with 24 Gy in three fractions. PD-1 blockade and α-OX40 were administered five times every other day. Flow cytometric analyses and immunohistochemistry were used to monitor subsequent changes in the immune cell repertoire. The combination of α-OX40, radiotherapy, and PD-1 blockade significantly improved primary tumor control, abscopal effects, and long-term survival beyond 2 months (60%). In the tumor microenvironment, the ratio of CD8+ T cells to CD4 + FOXP3+ regulatory T cells was significantly elevated and exhausted CD8+ T cells (PD-1+, CTLA-4+, TIM-3+, or LAG-3+ cells) were significantly reduced in the triple combination group. Systemically, α-OX40 co-stimulation and radiation significantly increased the CD103+ dendritic cell response in the spleen and plasma IFN-γ, respectively. Together, our results suggest that the combination of α-OX40 co-stimulation and radiation is a viable approach to overcome therapeutic resistance to PD-1 blockade in immunologically cold tumors, such as triple-negative breast cancer.
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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.