ArticleFrontiers in immunology2018
Anti-glucocorticoid-induced Tumor Necrosis Factor-Related Protein (GITR) Therapy Overcomes Radiation-Induced Treg Immunosuppression and Drives Abscopal Effects.
Article in Frontiers in immunology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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Who cites it
41 citing papers in PubMed, 63 citations in OpenAlex.
- The Double-Edged Sword: How Radiotherapy Shapes the Tumor Immune Microenvironment to Modulate Responses to Checkpoint Inhibitors.International journal of molecular sciences · 2026Review
- RUNX1 restrains STAT1-GITRL signaling to shape an immunosuppressive CRC microenvironment.Cell death discovery · 2026Article
- PD-1 inhibitor improves radiosensitivity by tumor vessel normalization.British journal of cancer · 2026Article
- Fluorescence tracking Treg movement identifies anti-CCR8 and radiation as a therapeutic combination.iScience · 2026Article
- Defining the abscopal effect in non-small cell lung cancer in the era of immunotherapy and lung ablation treatment: a narrative review.Frontiers in medicine · 2026Review
- Unlocking new frontiers: novel immune targets for next-generation cancer immunotherapy.Korean journal of clinical oncology · 2025Review
- Low-dose radiotherapy enhances the efficacy of PD-L1 blockade and induces the abscopal effect.Journal for immunotherapy of cancer · 2025Article
- G0S2: a potential target for NSCLC identified through prognostic models from multi-Omic analysis of regulatory T cell metabolic genes.NPJ precision oncology · 2025Article
- Molecular mechanisms underlying the abscopal effect induced by radiotherapy and its synergistic translational potential with immunotherapy.Therapeutic advances in medical oncology · 2025Review
- Emerging IO checkpoints in gastrointestinal oncology.Frontiers in immunology · 2025Review
- Infiltrating treg reprogramming in the tumor immune microenvironment and its optimization for immunotherapy.Biomarker research · 2024Review
- T Cell Features in Glioblastoma May Guide Therapeutic Strategies to Overcome Microenvironment Immunosuppression.Cancers · 2024Review
- Radiation-induced tumor immune microenvironments and potential targets for combination therapy.Signal transduction and targeted therapy · 2023Review
- Inhibition of STAT6 with Antisense Oligonucleotides Enhances the Systemic Antitumor Effects of Radiotherapy and Anti-PD-1 in Metastatic Non-Small Cell Lung Cancer.Cancer immunology research · 2023Article
- Quantitative systems pharmacology model of GITR-mediated T cell dynamics in tumor microenvironment.CPT: pharmacometrics & systems pharmacology · 2023Article
- Regulatory cells and the effect of cancer immunotherapy.Molecular cancer · 2023Review
- Shaping the Future of Immunotherapy Targets and Biomarkers in Melanoma and Non-Melanoma Cutaneous Cancers.International journal of molecular sciences · 2023Review
- A new target of radiotherapy combined with immunotherapy: regulatory T cells.Frontiers in immunology · 2023Review
- High-level of intratumoral GITR+ CD4 T cells associate with poor prognosis in gastric cancer.iScience · 2022Article
- A 'Hybrid' Radiotherapy Regimen Designed for Immunomodulation: Combining High-Dose Radiotherapy with Low-Dose Radiotherapy.Cancers · 2022Review
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Despite the potential to cure metastatic disease, immunotherapy on its own often fails outright or early on due to tumor immune evasion. To address this obstacle, we investigated combinations of anti-GITR, anti-PD1 and radiation therapy (XRT) in our previously developed anti-PD1 resistant 344SQ non-small cell lung adenocarcinoma preclinical tumor model. We hypothesized that targeting multiple mechanisms of immune evasion with this triple therapy would lead to an enhanced tumor-specific immune response and improve survival more so than any mono- or dual therapy. In a two tumor 344SQR murine model, treatment with anti-GITR, anti-PD1, and XRT led to significantly improved survival and an abscopal response, with half of the mice becoming tumor free. These mice showed durable response and increased CD4+ and CD8+ effector memory on tumor rechallenge. Regulatory T cells (Tregs) expressed the highest level of GITR at the tumor site and anti-GITR therapy drastically diminished Tregs at the tumor site. Anti-tumor effects were largely dependent on CD4+ T cells and partially dependent on CD8+ T cells. Anti-GITR IgG2a demonstrated superior efficacy to anti-GITR IgG1 in driving antitumor effects. Collectively, these results suggest that combinatorial strategies targeting multiple points of tumor immune evasion may lead to a robust and lasting antitumor response.
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