Investigation of the potential effects of estrogen receptor modulators on immune checkpoint molecules
Abstract Immune checkpoints regulate the immune system response. Recent studies suggest that flavonoids, known as phytoestrogens, may inhibit the PD-1/PD-L1 axis. We explored the potential of estrogens and 17 Selective Estrogen Receptor Modulators (SERMs) as inhibiting ligands for immune checkpoint...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2024-02-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-024-51804-2 |
| _version_ | 1797274977870807040 |
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| author | Nikita Abramenko Fréderic Vellieux Kateřina Veselá Zdeněk Kejík Jan Hajduch Michal Masařík Petr Babula David Hoskovec Karel Pacák Pavel Martásek Karel Smetana Milan Jakubek |
| author_facet | Nikita Abramenko Fréderic Vellieux Kateřina Veselá Zdeněk Kejík Jan Hajduch Michal Masařík Petr Babula David Hoskovec Karel Pacák Pavel Martásek Karel Smetana Milan Jakubek |
| author_sort | Nikita Abramenko |
| collection | DOAJ |
| description | Abstract Immune checkpoints regulate the immune system response. Recent studies suggest that flavonoids, known as phytoestrogens, may inhibit the PD-1/PD-L1 axis. We explored the potential of estrogens and 17 Selective Estrogen Receptor Modulators (SERMs) as inhibiting ligands for immune checkpoint proteins (CTLA-4, PD-L1, PD-1, and CD80). Our docking studies revealed strong binding energy values for quinestrol, quercetin, and bazedoxifene, indicating their potential to inhibit PD-1 and CTLA-4. Quercetin and bazedoxifene, known to modulate EGFR and IL-6R alongside estrogen receptors, can influence the immune checkpoint functionality. We discuss the impact of SERMs on PD-1 and CTLA-4, suggesting that these SERMs could have therapeutic effects through immune checkpoint inhibition. This study highlights the potential of SERMs as inhibitory ligands for immune checkpoint proteins, emphasizing the importance of considering PD-1 and CTLA-4 inhibition when evaluating SERMs as therapeutic agents. Our findings open new avenues for cancer immunotherapy by exploring the interaction between various SERMs and immune checkpoint pathways. |
| first_indexed | 2024-03-07T15:06:48Z |
| format | Article |
| id | doaj.art-031511e97a734e7a80fb86a3fbb5fcab |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-03-07T15:06:48Z |
| publishDate | 2024-02-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-031511e97a734e7a80fb86a3fbb5fcab2024-03-05T18:50:03ZengNature PortfolioScientific Reports2045-23222024-02-0114111410.1038/s41598-024-51804-2Investigation of the potential effects of estrogen receptor modulators on immune checkpoint moleculesNikita Abramenko0Fréderic Vellieux1Kateřina Veselá2Zdeněk Kejík3Jan Hajduch4Michal Masařík5Petr Babula6David Hoskovec7Karel Pacák8Pavel Martásek9Karel Smetana10Milan Jakubek11BIOCEV, First Faculty of Medicine, Charles UniversityBIOCEV, First Faculty of Medicine, Charles UniversityBIOCEV, First Faculty of Medicine, Charles UniversityBIOCEV, First Faculty of Medicine, Charles UniversityBIOCEV, First Faculty of Medicine, Charles UniversityBIOCEV, First Faculty of Medicine, Charles UniversityDepartment of Physiology, Faculty of Medicine, Masaryk University1st Department of Surgery-Department of Abdominal, Thoracic Surgery and Traumatology, First Faculty of Medicine, Charles University and General University HospitalSection on Medical Neuroendocrinology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of HealthDepartment of Paediatrics and Inherited Metabolic Disorders, First Faculty of Medicine, Charles University and General University HospitalBIOCEV, First Faculty of Medicine, Charles UniversityBIOCEV, First Faculty of Medicine, Charles UniversityAbstract Immune checkpoints regulate the immune system response. Recent studies suggest that flavonoids, known as phytoestrogens, may inhibit the PD-1/PD-L1 axis. We explored the potential of estrogens and 17 Selective Estrogen Receptor Modulators (SERMs) as inhibiting ligands for immune checkpoint proteins (CTLA-4, PD-L1, PD-1, and CD80). Our docking studies revealed strong binding energy values for quinestrol, quercetin, and bazedoxifene, indicating their potential to inhibit PD-1 and CTLA-4. Quercetin and bazedoxifene, known to modulate EGFR and IL-6R alongside estrogen receptors, can influence the immune checkpoint functionality. We discuss the impact of SERMs on PD-1 and CTLA-4, suggesting that these SERMs could have therapeutic effects through immune checkpoint inhibition. This study highlights the potential of SERMs as inhibitory ligands for immune checkpoint proteins, emphasizing the importance of considering PD-1 and CTLA-4 inhibition when evaluating SERMs as therapeutic agents. Our findings open new avenues for cancer immunotherapy by exploring the interaction between various SERMs and immune checkpoint pathways.https://doi.org/10.1038/s41598-024-51804-2 |
| spellingShingle | Nikita Abramenko Fréderic Vellieux Kateřina Veselá Zdeněk Kejík Jan Hajduch Michal Masařík Petr Babula David Hoskovec Karel Pacák Pavel Martásek Karel Smetana Milan Jakubek Investigation of the potential effects of estrogen receptor modulators on immune checkpoint molecules Scientific Reports |
| title | Investigation of the potential effects of estrogen receptor modulators on immune checkpoint molecules |
| title_full | Investigation of the potential effects of estrogen receptor modulators on immune checkpoint molecules |
| title_fullStr | Investigation of the potential effects of estrogen receptor modulators on immune checkpoint molecules |
| title_full_unstemmed | Investigation of the potential effects of estrogen receptor modulators on immune checkpoint molecules |
| title_short | Investigation of the potential effects of estrogen receptor modulators on immune checkpoint molecules |
| title_sort | investigation of the potential effects of estrogen receptor modulators on immune checkpoint molecules |
| url | https://doi.org/10.1038/s41598-024-51804-2 |
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