Metabolic reprogramming by adenosine antagonism and implications in non-small cell lung cancer therapy
Non-small cell lung cancer (NSCLC) is a heterogeneous disease with genetic and environmental parameters that influence cell metabolism. Because of the complex interplay of environmental factors within the tumor microenvironment (TME) and the profound impact of these factors on the metabolic activiti...
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| Format: | Article |
| Language: | English |
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Elsevier
2022-10-01
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| Series: | Neoplasia: An International Journal for Oncology Research |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S1476558622000513 |
| _version_ | 1811281283920166912 |
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| author | Shuxiao Guan Shankar Suman Joseph M. Amann Ruohan Wu David P. Carbone Jie Wang Mikhail M. Dikov |
| author_facet | Shuxiao Guan Shankar Suman Joseph M. Amann Ruohan Wu David P. Carbone Jie Wang Mikhail M. Dikov |
| author_sort | Shuxiao Guan |
| collection | DOAJ |
| description | Non-small cell lung cancer (NSCLC) is a heterogeneous disease with genetic and environmental parameters that influence cell metabolism. Because of the complex interplay of environmental factors within the tumor microenvironment (TME) and the profound impact of these factors on the metabolic activities of tumor and immune cells, there is an emerging interest to advance the understanding of these diverse metabolic phenotypes in the TME. High levels of adenosine are characteristic of the TME, and adenosine can have a significant impact on both tumor cell growth and the immune response. Consistent with this, we showed in NSCLC data from TCGA that high expression of the A2BR leads to worse outcome and that expression of A2BR may be different for different mutation backgrounds. We then investigated the metabolic reprogramming of tumor cells and immune cells (T and dendritic cells) by adenosine. We used A2AR and A2BR antagonism or agonism as well as receptor knockout animals to explore whether these treatments altered specific immune compartments or conferred specific therapeutic vulnerabilities. Using the seahorse assay, we found that an A2BR antagonist modulates oxidative stress homeostasis in NSCLC cell lines. In addition, we found distinct metabolic roles of A2AR and A2BR receptors in T cell activation and dendritic cell maturation. These data suggest potential mechanisms and therapeutic benefits of A2 receptor antagonist therapy in NSCLC. |
| first_indexed | 2024-04-13T01:29:48Z |
| format | Article |
| id | doaj.art-4a963ce351344119989cab46eeb0fe16 |
| institution | Directory Open Access Journal |
| issn | 1476-5586 |
| language | English |
| last_indexed | 2024-04-13T01:29:48Z |
| publishDate | 2022-10-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Neoplasia: An International Journal for Oncology Research |
| spelling | doaj.art-4a963ce351344119989cab46eeb0fe162022-12-22T03:08:32ZengElsevierNeoplasia: An International Journal for Oncology Research1476-55862022-10-0132100824Metabolic reprogramming by adenosine antagonism and implications in non-small cell lung cancer therapyShuxiao Guan0Shankar Suman1Joseph M. Amann2Ruohan Wu3David P. Carbone4Jie Wang5Mikhail M. Dikov6National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China; The James Comprehensive Cancer Center, Ohio State University, Columbus, OH, United States; Corresponding author at: National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China; The James Comprehensive Cancer Center, Ohio State University, Columbus, OH.The James Comprehensive Cancer Center, Ohio State University, Columbus, OH, United StatesThe James Comprehensive Cancer Center, Ohio State University, Columbus, OH, United StatesThe James Comprehensive Cancer Center, Ohio State University, Columbus, OH, United StatesThe James Comprehensive Cancer Center, Ohio State University, Columbus, OH, United StatesNational Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China; State Key Laboratory of Molecular Oncology, Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China; Corresponding author at: State Key Laboratory of Molecular Oncology, Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China.The James Comprehensive Cancer Center, Ohio State University, Columbus, OH, United StatesNon-small cell lung cancer (NSCLC) is a heterogeneous disease with genetic and environmental parameters that influence cell metabolism. Because of the complex interplay of environmental factors within the tumor microenvironment (TME) and the profound impact of these factors on the metabolic activities of tumor and immune cells, there is an emerging interest to advance the understanding of these diverse metabolic phenotypes in the TME. High levels of adenosine are characteristic of the TME, and adenosine can have a significant impact on both tumor cell growth and the immune response. Consistent with this, we showed in NSCLC data from TCGA that high expression of the A2BR leads to worse outcome and that expression of A2BR may be different for different mutation backgrounds. We then investigated the metabolic reprogramming of tumor cells and immune cells (T and dendritic cells) by adenosine. We used A2AR and A2BR antagonism or agonism as well as receptor knockout animals to explore whether these treatments altered specific immune compartments or conferred specific therapeutic vulnerabilities. Using the seahorse assay, we found that an A2BR antagonist modulates oxidative stress homeostasis in NSCLC cell lines. In addition, we found distinct metabolic roles of A2AR and A2BR receptors in T cell activation and dendritic cell maturation. These data suggest potential mechanisms and therapeutic benefits of A2 receptor antagonist therapy in NSCLC.http://www.sciencedirect.com/science/article/pii/S1476558622000513Non-small cell lung cancerTumor and immune cellsGene mutationA2AR/A2BR antagonistTumor microenvironmentMetabolism |
| spellingShingle | Shuxiao Guan Shankar Suman Joseph M. Amann Ruohan Wu David P. Carbone Jie Wang Mikhail M. Dikov Metabolic reprogramming by adenosine antagonism and implications in non-small cell lung cancer therapy Neoplasia: An International Journal for Oncology Research Non-small cell lung cancer Tumor and immune cells Gene mutation A2AR/A2BR antagonist Tumor microenvironment Metabolism |
| title | Metabolic reprogramming by adenosine antagonism and implications in non-small cell lung cancer therapy |
| title_full | Metabolic reprogramming by adenosine antagonism and implications in non-small cell lung cancer therapy |
| title_fullStr | Metabolic reprogramming by adenosine antagonism and implications in non-small cell lung cancer therapy |
| title_full_unstemmed | Metabolic reprogramming by adenosine antagonism and implications in non-small cell lung cancer therapy |
| title_short | Metabolic reprogramming by adenosine antagonism and implications in non-small cell lung cancer therapy |
| title_sort | metabolic reprogramming by adenosine antagonism and implications in non small cell lung cancer therapy |
| topic | Non-small cell lung cancer Tumor and immune cells Gene mutation A2AR/A2BR antagonist Tumor microenvironment Metabolism |
| url | http://www.sciencedirect.com/science/article/pii/S1476558622000513 |
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