Radiotherapy Combined with PD-1 Inhibition Increases NK Cell Cytotoxicity towards Nasopharyngeal Carcinoma Cells
Background: Nasopharyngeal carcinoma (NPC) in endemic regions and younger patients is characterized by a prominent lymphomononuclear infiltration. Radiation is the principal therapeutic modality for patients with NPC. Recent data suggest that the efficacy of radiotherapy in various cancers can be au...
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MDPI AG
2021-09-01
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| Online Access: | https://www.mdpi.com/2073-4409/10/9/2458 |
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| author | Anna Makowska Nora Lelabi Christina Nothbaum Lian Shen Pierre Busson Tram Thi Bao Tran Michael Eble Udo Kontny |
| author_facet | Anna Makowska Nora Lelabi Christina Nothbaum Lian Shen Pierre Busson Tram Thi Bao Tran Michael Eble Udo Kontny |
| author_sort | Anna Makowska |
| collection | DOAJ |
| description | Background: Nasopharyngeal carcinoma (NPC) in endemic regions and younger patients is characterized by a prominent lymphomononuclear infiltration. Radiation is the principal therapeutic modality for patients with NPC. Recent data suggest that the efficacy of radiotherapy in various cancers can be augmented when combined with immune checkpoint blockade. Here, we investigate the effect of radiotherapy on the killing of NPC cells by Natural Killer (NK) cells. Methods: NPC cell lines and a patient-derived xenograft were exposed to NK cells in the context of radiotherapy. Cytotoxicity was measured using the calcein-release assay. The contribution of the PD-L1/PD-1 checkpoint and signaling pathways to killing were analyzed using specific inhibitors. Results: Radiotherapy sensitized NPC cells to NK cell killing and upregulated expression of PD-1 ligand (PD-L1) in NPC cells and PD-1 receptor (PD-1) in NK cells. Blocking of the PD-L1/PD-1 checkpoint further increased the killing of NPC cells by NK cells in the context of radiotherapy. Conclusion: Radiation boosts the killing of NPC cells by NK cells. Killing can be further augmented by blockade of the PD-L1/PD-1 checkpoint. The combination of radiotherapy with PD-L1/PD-1 checkpoint blockade could therefore increase the efficacy of radiotherapy in NPC tumors. |
| first_indexed | 2024-03-10T07:48:14Z |
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| id | doaj.art-463900eed4c74c8f91ccfd9dabd3cb22 |
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| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-10T07:48:14Z |
| publishDate | 2021-09-01 |
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| spelling | doaj.art-463900eed4c74c8f91ccfd9dabd3cb222023-11-22T12:26:32ZengMDPI AGCells2073-44092021-09-01109245810.3390/cells10092458Radiotherapy Combined with PD-1 Inhibition Increases NK Cell Cytotoxicity towards Nasopharyngeal Carcinoma CellsAnna Makowska0Nora Lelabi1Christina Nothbaum2Lian Shen3Pierre Busson4Tram Thi Bao Tran5Michael Eble6Udo Kontny7Division of Pediatric Hematology, Oncology and Stem Cell Transplantation, Medical Faculty, Rhenish-Westphalian Technical University, 52074 Aachen, GermanyDivision of Pediatric Hematology, Oncology and Stem Cell Transplantation, Medical Faculty, Rhenish-Westphalian Technical University, 52074 Aachen, GermanyDivision of Pediatric Hematology, Oncology and Stem Cell Transplantation, Medical Faculty, Rhenish-Westphalian Technical University, 52074 Aachen, GermanyDivision of Pediatric Hematology, Oncology and Stem Cell Transplantation, Medical Faculty, Rhenish-Westphalian Technical University, 52074 Aachen, GermanyCNRS UMR 8126, Gustave Roussy, Université Paris Sud, Université Paris-Saclay, 94805 Villejuif, FranceCNRS UMR 8126, Gustave Roussy, Université Paris Sud, Université Paris-Saclay, 94805 Villejuif, FranceDepartment of Radiation Oncology, Medical Faculty, Rhenish-Westphalian Technical University, 52074 Aachen, GermanyDivision of Pediatric Hematology, Oncology and Stem Cell Transplantation, Medical Faculty, Rhenish-Westphalian Technical University, 52074 Aachen, GermanyBackground: Nasopharyngeal carcinoma (NPC) in endemic regions and younger patients is characterized by a prominent lymphomononuclear infiltration. Radiation is the principal therapeutic modality for patients with NPC. Recent data suggest that the efficacy of radiotherapy in various cancers can be augmented when combined with immune checkpoint blockade. Here, we investigate the effect of radiotherapy on the killing of NPC cells by Natural Killer (NK) cells. Methods: NPC cell lines and a patient-derived xenograft were exposed to NK cells in the context of radiotherapy. Cytotoxicity was measured using the calcein-release assay. The contribution of the PD-L1/PD-1 checkpoint and signaling pathways to killing were analyzed using specific inhibitors. Results: Radiotherapy sensitized NPC cells to NK cell killing and upregulated expression of PD-1 ligand (PD-L1) in NPC cells and PD-1 receptor (PD-1) in NK cells. Blocking of the PD-L1/PD-1 checkpoint further increased the killing of NPC cells by NK cells in the context of radiotherapy. Conclusion: Radiation boosts the killing of NPC cells by NK cells. Killing can be further augmented by blockade of the PD-L1/PD-1 checkpoint. The combination of radiotherapy with PD-L1/PD-1 checkpoint blockade could therefore increase the efficacy of radiotherapy in NPC tumors.https://www.mdpi.com/2073-4409/10/9/2458nasopharyngeal carcinomanatural killer cellsprogrammed cell death ligand 1radiotherapynuclear factor kappa Binterferon-beta |
| spellingShingle | Anna Makowska Nora Lelabi Christina Nothbaum Lian Shen Pierre Busson Tram Thi Bao Tran Michael Eble Udo Kontny Radiotherapy Combined with PD-1 Inhibition Increases NK Cell Cytotoxicity towards Nasopharyngeal Carcinoma Cells Cells nasopharyngeal carcinoma natural killer cells programmed cell death ligand 1 radiotherapy nuclear factor kappa B interferon-beta |
| title | Radiotherapy Combined with PD-1 Inhibition Increases NK Cell Cytotoxicity towards Nasopharyngeal Carcinoma Cells |
| title_full | Radiotherapy Combined with PD-1 Inhibition Increases NK Cell Cytotoxicity towards Nasopharyngeal Carcinoma Cells |
| title_fullStr | Radiotherapy Combined with PD-1 Inhibition Increases NK Cell Cytotoxicity towards Nasopharyngeal Carcinoma Cells |
| title_full_unstemmed | Radiotherapy Combined with PD-1 Inhibition Increases NK Cell Cytotoxicity towards Nasopharyngeal Carcinoma Cells |
| title_short | Radiotherapy Combined with PD-1 Inhibition Increases NK Cell Cytotoxicity towards Nasopharyngeal Carcinoma Cells |
| title_sort | radiotherapy combined with pd 1 inhibition increases nk cell cytotoxicity towards nasopharyngeal carcinoma cells |
| topic | nasopharyngeal carcinoma natural killer cells programmed cell death ligand 1 radiotherapy nuclear factor kappa B interferon-beta |
| url | https://www.mdpi.com/2073-4409/10/9/2458 |
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