ArticleOncotarget2017
Radiation alters PD-L1/NKG2D ligand levels in lung cancer cells and leads to immune escape from NK cell cytotoxicity via IL-6-MEK/Erk signaling pathway.
Article in Oncotarget, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers, 1 of them a synthesis that pooled it.
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Who cites it
50 citing papers in PubMed, 1 synthesis or guideline pooled it, 72 citations in OpenAlex.
- Modulation of tumor-associated macrophage activity with radiation therapy: a systematic review.Strahlentherapie und Onkologie : Organ der Deutschen Rontgengesellschaft ... [et al] · 2023Pooled it
- Newcastle Disease Virus - Induced Interferons Regulate PD-L1 and MICA Expression in Human Tumor and Normal Cells.ImmunoTargets and therapy · 2026Article
- PRDM1 Is Associated with Chemoradiotherapy-Associated Enrichment of Adaptive NK Cells in Cervical Cancer.Computational and structural biotechnology journal · 2026Article
- Investigating T Cell Immune Dynamics and IL-6's Duality in a Microfluidic Lung Tumor Model.ACS applied materials & interfaces · 2025Article
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- Hyperthermia in Combination with Emerging Targeted and Immunotherapies as a New Approach in Cancer Treatment.Cancers · 2024Review
- The expression mechanism of programmed cell death 1 ligand 1 and its role in immunomodulatory ability of mesenchymal stem cells.Chinese journal of traumatology = Zhonghua chuang shang za zhi · 2024Review
- Immunotherapy and biomarkers in patients with lung cancer with tuberculosis: Recent advances and future Directions.iScience · 2023Review
- End-Stage Idiopathic Pulmonary Fibrosis Lung Microenvironment Promotes Impaired NK Activity.Journal of immunology (Baltimore, Md. : 1950) · 2023Article
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- CAR T cell-based immunotherapy and radiation therapy: potential, promises and risks.Molecular cancer · 2023Review
- Metabolic Reprogramming of NK Cells by Black Phosphorus Quantum Dots Potentiates Cancer Immunotherapy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
- Association between PD-L1 and Ki-67 expression and clinicopathologic features in NSCLC patients.American journal of translational research · 2023Article
- Charting a killer course to the solid tumor: strategies to recruit and activate NK cells in the tumor microenvironment.Frontiers in immunology · 2023Review
- Tumor immune checkpoints and their associated inhibitors.Journal of Zhejiang University. Science. B · 2022Review
- Review
- Improvement of the anticancer efficacy of PD-1/PD-L1 blockade via combination therapy and PD-L1 regulation.Journal of hematology & oncology · 2022Review
- Immune marker expression of irradiated mesothelioma cell lines.Frontiers in oncology · 2022Article
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
Abstract
We investigated whether radiation influences the susceptibility of non-small cell lung cancer (NSCLC) cells to NK cell mediated cytotoxicity. We found radiation treatment increased expression of programmed cell death ligand 1 (PD-L1), but decreased NK group 2, member D (NKG2D) ligand expressions in A549 and H157 NSCLC cells. Both types of changes would have protected tumor cells from the cytotoxic action of NK cells. Consistently, we detected similar alteration in these molecules in radioresistant A549R26-1 and H157R24-1 subline cells. Higher PD-L1 level was also observed in tumors of A549R26-1 cell-derived xenografts than tumors of parental A549 (A549P) cell-derived xenografts. Accordingly, we found radioresistant cells were more resistant to the cytotoxic action of NK cells than parental cells, and such resistance was decreased when neutralizing antibody (Ab) of PD-L1 was added to the radioresistant cell/NK cell co-cultures. In mechanism studies, we found that IL-6-MEK/Erk signaling contributed most significantly to the up-regulation of PD-L1/down-regulation of NKG2D ligands in radioresistant cells. The addition of the MEK/Erk inhibitor increased the susceptibility of A549R26-1 and H157R24-1 cells to NK-cell cytotoxicity while no significant effect was observed in parental cells. Moreover, we detected enhanced NK-cell cytotoxicity to radioresistant cells when PD-L1 Ab and MEK/Erk inhibitor were added together to co-cultures of tumor/NK cells compared to when PD-L1 Ab was used alone. We suggest that combined use of PD-L1 Ab and MEK/Erk inhibitor may offer better therapeutic benefits than PD-L1 Ab alone to treat NSCLC patients who are receiving radiotherapy or who are at the radioresistant stage.
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