دورية أكاديمية
Clearance of senescent macrophages ameliorates tumorigenesis in KRAS-driven lung cancer.
| العنوان: | Clearance of senescent macrophages ameliorates tumorigenesis in KRAS-driven lung cancer. |
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| المؤلفون: | Haston, Scott, Gonzalez-Gualda, Estela, Morsli, Samir, Ge, Jianfeng, Reen, Virinder, Calderwood, Alexander, Moutsopoulos, Ilias, Panousopoulos, Leonidas, Deletic, Polina, Carreno, Gabriela, Guiho, Romain, Manshaei, Saba, Gonzalez-Meljem, Jose Mario, Lim, Hui Yuan, Simpson, Daniel J, Birch, Jodie, Pallikonda, Husayn A, Chandra, Tamir, Macias, David, Doherty, Gary J, Rassl, Doris M, Rintoul, Robert C, Signore, Massimo, Mohorianu, Irina, Akbar, Arne N, Gil, Jesús, Muñoz-Espín, Daniel, Martinez-Barbera, Juan Pedro |
| بيانات النشر: | Elsevier BV Department of Oncology //dx.doi.org/10.1016/j.ccell.2023.05.004 Cancer Cell |
| سنة النشر: | 2023 |
| المجموعة: | Apollo - University of Cambridge Repository |
| مصطلحات موضوعية: | ABT-737, NSCLC, aging, cancer, endothelial cells, immunosuppression, macrophages, p16INK4a, senescence, senolytic, Aged, Animals, Humans, Mice, Carcinogenesis, Cellular Senescence, Lung Neoplasms, Proto-Oncogene Proteins p21(ras), Tumor Microenvironment |
| الوصف: | The accumulation of senescent cells in the tumor microenvironment can drive tumorigenesis in a paracrine manner through the senescence-associated secretory phenotype (SASP). Using a new p16-FDR mouse line, we show that macrophages and endothelial cells are the predominant senescent cell types in murine KRAS-driven lung tumors. Through single cell transcriptomics, we identify a population of tumor-associated macrophages that express a unique array of pro-tumorigenic SASP factors and surface proteins and are also present in normal aged lungs. Genetic or senolytic ablation of senescent cells, or macrophage depletion, result in a significant decrease in tumor burden and increased survival in KRAS-driven lung cancer models. Moreover, we reveal the presence of macrophages with senescent features in human lung pre-malignant lesions, but not in adenocarcinomas. Taken together, our results have uncovered the important role of senescent macrophages in the initiation and progression of lung cancer, highlighting potential therapeutic avenues and cancer preventative strategies. |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | application/pdf |
| اللغة: | English |
| العلاقة: | https://www.repository.cam.ac.uk/handle/1810/362100Test |
| الإتاحة: | https://www.repository.cam.ac.uk/handle/1810/362100Test |
| حقوق: | Attribution 4.0 International ; https://creativecommons.org/licenses/by/4.0Test/ |
| رقم الانضمام: | edsbas.FFB2EE75 |
| قاعدة البيانات: | BASE |
| الوصف غير متاح. |