ArticleScientific reports2022
ICOS is upregulated on T cells following radiation and agonism combined with radiation results in enhanced tumor control.
Article in Scientific reports, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 20 citations in OpenAlex.
- Fluorescence tracking CD8 T cells from tumor-draining lymph nodes to irradiated tumors and their activation in the tumor environment.Journal of immunology (Baltimore, Md. : 1950) · 2026Article
- Review
- Cord blood-derived iNK T cells as a platform for allogeneic CAR T cell therapy.Frontiers in immunology · 2025Article
- Future investigative directions for novel therapeutic targets in head and neck cancer.Expert review of anticancer therapy · 2024Review
- Fluorescence tracking demonstrates T cell recirculation is transiently impaired by radiation therapy to the tumor.Scientific reports · 2024Article
- Investigation of activation-induced markers (AIM) in porcine T cells by flow cytometry.Frontiers in veterinary science · 2024Article
- 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
- Integrated systems immunology approach identifies impaired effector T cell memory responses as a feature of progression to severe dengue fever.Journal of biomedical science · 2023Article
- The immunogenic radiation and new players in immunotherapy and targeted therapy for head and neck cancer.Frontiers in oral health · 2023Review
- Differential expression of CCR8 in tumors versus normal tissue allows specific depletion of tumor-infiltrating T regulatory cells by GS-1811, a novel Fc-optimized anti-CCR8 antibody.Oncoimmunology · 2022Article
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
Multiple preclinical studies have shown improved outcomes when radiation therapy is combined with immune modulating antibodies. However, to date, many of these promising results have failed to translate to successful clinical studies. This led us to explore additional checkpoint and co-stimulatory pathways that may be regulated by radiation therapy. Here, we demonstrate that radiation increases the expression of inducible T cell co-stimulator (ICOS) on both CD4 and CD8 T cells in the blood following treatment. Moreover, when we combined a novel ICOS agonist antibody with radiation we observed durable cures across multiple tumor models and mouse strains. Depletion studies revealed that CD8 T cells were ultimately required for treatment efficacy, but CD4 T cells and NK cells also partially contributed to tumor control. Phenotypic analysis showed that the combination therapy diminished the increased infiltration of regulatory T cells into the tumor that typically occurs following radiation alone. Finally, we demonstrate in a poorly immunogenic pancreatic tumor model which is resistant to combined radiation and anti-PD1 checkpoint blockade that the addition of this novel ICOS agonist antibody to the treatment regimen results in tumor control. These findings identify ICOS as part of a T cell pathway that is modulated by radiation and targeting this pathway with a novel ICOS antibody results in durable tumor control in preclinical models.
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