ArticleThe Journal of clinical investigation2024
PD-1 or CTLA-4 blockade promotes CD86-driven Treg responses upon radiotherapy of lymphocyte-depleted cancer in mice.
Article in The Journal of clinical investigation, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
What it found
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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
21 citing papers in PubMed, 24 citations in OpenAlex.
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- Insufficient ferroptosis in radiation-induced tumor cells promote Treg cell generation to induce radiotherapy resistance.Communications biology · 2026Article
- Targeting tumor-specific T cells with LAG3-directed interleukin-2 prevents T-cell exhaustion and reinvigorates antitumor immunity.Signal transduction and targeted therapy · 2026Article
- Regulatory T cells in cancer and inflammation.Signal transduction and targeted therapy · 2026Review
- Stem-like PD-1Journal for immunotherapy of cancer · 2026Article
- Gut microbiome-driven modulation of the tumor immune microenvironment optimizes dual checkpoint blockade in advanced non-small-cell lung cancer.ESMO open · 2026Article
- Regulatory T cells in breast cancer drivers of immune suppression and targets for immunotherapy.Frontiers in immunology · 2026Review
- Effect of lymph node dissection numbers after conversion immunochemotherapy on the survival of gastric cancer patients: a multi-center retrospective study.Frontiers in immunology · 2026Observational
- The resilient subset: cancer stem cells at the core of immunotherapy resistance.Immunotherapy advances · 2026Review
- CCL5-Mediated Immune Interactions Drive Osteosarcoma Progression: Insights from Mendelian Randomization, Single-Cell Analysis, and Functional Validation.Journal of inflammation research · 2026Article
- Radiation therapy causes a STING and MyD88-independent upregulation of CD80 and CD86 in macrophages and monocytes that limits tumor control.Cancer immunology, immunotherapy : CII · 2025Article
- SPP1 + macrophage and Treg interaction mediates immunosuppression and adverse survival in HER2 + breast cancer.Scientific reports · 2025Article
- Roles of the phagocytosis checkpoint in radiotherapy.Cell death & disease · 2025Review
- Beyond the Limits: How Is Spectral Flow Cytometry Reshaping the Clinical Landscape and What Is Coming Next?Cells · 2025Review
- Bolstering CD8Biology · 2025Review
- Faecalcrobiota metabolites: emerging insights into cancer radiotherapy outcomes.Frontiers in microbiology · 2025Review
- Immunosuppressive mechanisms and therapeutic targeting of regulatory T cells in ovarian cancer.Frontiers in immunology · 2025Review
- Revisiting Tregs in cancer and beyond: immunological control and therapeutic potential.Frontiers in immunology · 2025Review
- Current trends in sensitizing immune checkpoint inhibitors for cancer treatment.Molecular cancer · 2024Review
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Radiotherapy (RT) is considered immunogenic, but clinical data demonstrating RT-induced T cell priming are scarce. Here, we show in a mouse tumor model representative of human lymphocyte-depleted cancer that RT enhanced spontaneous priming of thymus-derived (FOXP3+Helios+) Tregs by the tumor. These Tregs acquired an effector phenotype, populated the tumor, and impeded tumor control by a simultaneous, RT-induced CD8+ cytotoxic T cell (CTL) response. Combination of RT with CTLA-4 or PD-1 blockade, which enables CD28 costimulation, further increased this Treg response and failed to improve tumor control. We discovered that upon RT, the CD28 ligands CD86 and CD80 differentially affected the Treg response. CD86, but not CD80, blockade prevented the effector Treg response, enriched the tumor-draining lymph node migratory conventional DCs that were positive for PD-L1 and CD80 (PD-L1+CD80+), and promoted CTL priming. Blockade of CD86 alone or in combination with PD-1 enhanced intratumoral CTL accumulation, and the combination significantly increased RT-induced tumor regression and OS. We advise that combining RT with PD-1 and/or CTLA-4 blockade may be counterproductive in lymphocyte-depleted cancers, since these interventions drive Treg responses in this context. However, combining RT with CD86 blockade may promote the control of such tumors by enabling a CTL response.
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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.