ArticleProceedings of the National Academy of Sciences of the United States of America2022
Radiotherapy transiently reduces the sensitivity of cancer cells to lymphocyte cytotoxicity.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers, 1 of them a synthesis 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.
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Who cites it
17 citing papers in PubMed, 1 synthesis or guideline pooled it, 31 citations in OpenAlex.
- Pooled it
- Differential perforin sensitivity drives lineage-dependent resistance to CAR T-cell killing in blood cancer cell lines.Blood advances · 2026Article
- Radiotherapy and Immune System Interactions Historical Perspectives and Clinical Advancements.Molecular carcinogenesis · 2026Review
- HLA-E as an Emerging Checkpoint and Biomarker in Personalized Cancer Immunotherapy.Current medical science · 2026Review
- An immunostimulant nanomedicine enhances radioimmunotherapy by remodeling the tumor immunosuppressive landscape after radiotherapy.Acta pharmaceutica Sinica. B · 2026Article
- The Proimmunomodulatory and Anti-immunomodulatory Effects of Radiotherapy in Oncologic Care.Hematology/oncology clinics of North America · 2025Review
- Synthetic reprogramming of tumor cell fate for modulating radiotherapy-induced dynamic responses: perspectives on radiosensitizing and immunoregulatory effects.Theranostics · 2025Review
- Membrane Lipid Replacement for reconstituting mitochondrial function and moderating cancer-related fatigue, pain and other symptoms while counteracting the adverse effects of cancer cytotoxic therapy.Clinical & experimental metastasis · 2024Review
- Intensified NK cell therapy in combination with low-dose chemoradiotherapy against human colorectal cancer.Cancer immunology, immunotherapy : CII · 2023Article
- Machine learning identifies multi-parametric functional PET/MR imaging cluster to predict radiation resistance in preclinical head and neck cancer models.European journal of nuclear medicine and molecular imaging · 2023Article
- Radiation-induced tumor immune microenvironments and potential targets for combination therapy.Signal transduction and targeted therapy · 2023Review
- Harnessing the Immunological Effects of Radiation to Improve Immunotherapies in Cancer.International journal of molecular sciences · 2023Review
- Charting a killer course to the solid tumor: strategies to recruit and activate NK cells in the tumor microenvironment.Frontiers in immunology · 2023Review
- Updates on radiotherapy-immunotherapy combinations: Proceedings of 6Oncoimmunology · 2023Review
- A review on lymphocyte radiosensitivity and its impact on radiotherapy.Frontiers in oncology · 2023Review
- Disruption of the NKG2A:HLA-E Immune Checkpoint Axis to Enhance NK Cell Activation against Cancer.Vaccines · 2022Review
- Escaping Death: How Cancer Cells and Infected Cells Resist Cell-Mediated Cytotoxicity.Frontiers in immunology · 2022Review
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 2 countries.
Funding
Abstract
The impact of radiotherapy on the interaction between immune cells and cancer cells is important not least because radiotherapy can be used alongside immunotherapy as a cancer treatment. Unexpectedly, we found that X-ray irradiation of cancer cells induced significant resistance to natural killer (NK) cell killing. This was true across a wide variety of cancer-cell types as well as for antibody-dependent cellular cytotoxicity. Resistance appeared 72 h postirradiation and persisted for 2 wk. Resistance could also occur independently of radiotherapy through pharmacologically induced cell-cycle arrest. Crucially, multiple steps in NK-cell engagement, synapse assembly, and activation were unaffected by target cell irradiation. Instead, radiotherapy caused profound resistance to perforin-induced calcium flux and lysis. Resistance also occurred to a structurally similar bacterial toxin, streptolysin O. Radiotherapy did not affect the binding of pore-forming proteins at the cell surface or membrane repair. Rather, irradiation instigated a defect in functional pore formation, consistent with phosphatidylserine-mediated perforin inhibition. In vivo, radiotherapy also led to a significant reduction in NK cell-mediated clearance of cancer cells. Radiotherapy-induced resistance to perforin also constrained chimeric antigen receptor T-cell cytotoxicity. Together, these data establish a treatment-induced resistance to lymphocyte cytotoxicity that is important to consider in the design of radiotherapy-immunotherapy protocols.
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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.