ArticleThe Journal of clinical investigation2019
Type I IFN protects cancer cells from CD8+ T cell-mediated cytotoxicity after radiation.
Article in The Journal of clinical investigation, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 89 papers, 2 of them syntheses that pooled it.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
89 citing papers in PubMed, 2 syntheses or guidelines pooled it, 127 citations in OpenAlex.
- Synergies between radiotherapy and immunotherapy: a systematic review from mechanism to clinical application.Frontiers in immunology · 2025Pooled it
- Bridging Radiotherapy to Immunotherapy: The IFN-JAK-STAT Axis.International journal of molecular sciences · 2021Pooled it
- Radiotherapy and immunotherapy in cancer treatment: mechanisms of clinical synergy.The Journal of clinical investigation · 2026Review
- Radiotherapy and cytokines: A systems view of immunotherapy and toxicity (Review).International journal of molecular medicine · 2026Review
- Developmental programmes drive cellular plasticity, disease progression and therapy resistance in lung adenocarcinoma.Molecular oncology · 2026Article
- Single-cell profiling of tumor lineage plasticity and the immune microenvironment in transformed small cell lung cancer.Journal of translational medicine · 2026Article
- Interferon signaling pathways in health and disease.Molecular biomedicine · 2025Review
- Context-dependent impact of type I interferon signaling in cancer.Molecular cancer · 2025Review
- Polio virotherapy provokes MDA5 signaling and CD4Microbiology and molecular biology reviews : MMBR · 2025Review
- Oxidative Stress and Inflammation: Drivers of Tumorigenesis and Therapeutic Opportunities.Antioxidants (Basel, Switzerland) · 2025Review
- Immunological Effects of Proton Radiotherapy: New Opportunities and Challenges in Cancer Therapy.Cancer innovation · 2025Review
- The Proimmunomodulatory and Anti-immunomodulatory Effects of Radiotherapy in Oncologic Care.Hematology/oncology clinics of North America · 2025Review
- Low-dose irradiation of the gut improves the efficacy of PD-L1 blockade in metastatic cancer patients.Cancer cell · 2025Article
- Cytokines in cancer.Cancer cell · 2025Review
- Research progress on immunotherapy combined with neoadjuvant concurrent chemoradiotherapy in pMMR/MSS locally advanced rectal cancer.Frontiers in immunology · 2025Review
- X-ray-responsive dissolving microneedles mediate STING pathway activation to potentiate cutaneous melanoma radio-immunotherapy.Theranostics · 2025Article
- Radio-chemotherapy and metformin selectively modulate the heterogeneous landscape of glioma with ribosome biogenesis, long non coding RNA and immune-escape markers as major player.International journal of biological sciences · 2025Article
- Strategies for overcoming tumour resistance to immunotherapy: harnessing the power of radiation therapy.The British journal of radiology · 2024Review
- Radiotherapy and immunology.The Journal of experimental medicine · 2024Review
- Review
29 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
Abstract
Treatment of tumors with ionizing radiation stimulates an antitumor immune response partly dependent on induction of IFNs. These IFNs directly enhance dendritic cell and CD8+ T cell activity. Here we show that resistance to an effective antitumor immune response is also a result of IFN signaling in a different cellular compartment of the tumor, the cancer cells themselves. We abolished type I IFN signaling in cancer cells by genetic elimination of its receptor, IFNAR1. Pronounced immune responses were provoked after ionizing radiation of tumors from 4 mouse cancer cell lines with Ifnar1 knockout. This enhanced response depended on CD8+ T cells and was mediated by enhanced susceptibility to T cell-mediated killing. Induction of Serpinb9 proved to be the mechanism underlying control of susceptibility to T cell killing after radiation. Ifnar1-deficient tumors had an augmented response to anti-PD-L1 immunotherapy with or without radiation. We conclude that type I IFN can protect cancer cells from T cell-mediated cytotoxicity through regulation of Serpinb9. This result helps explain why radiation of tumors can stimulate antitumor immunity yet also result in resistance. It further suggests potential targets for intervention to improve therapy and to predict responses.
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What OpenQuestion holds
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.