دورية أكاديمية
Co-inhibition of TGF-β and PD-L1 pathways in a metastatic colorectal cancer mouse model triggers interferon responses, innate cells and T cells, alongside metabolic changes and tumor resistance
| العنوان: | Co-inhibition of TGF-β and PD-L1 pathways in a metastatic colorectal cancer mouse model triggers interferon responses, innate cells and T cells, alongside metabolic changes and tumor resistance |
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| المؤلفون: | Nair, Reshmi, Lannagan, Tamsin R.M., Jackstadt, Rene, Andrusaite, Anna, Cole, John, Boyne, Caitlin, Nibbs, Robert J.B., Sansom, Owen J., Milling, Simon |
| بيانات النشر: | Taylor & Francis |
| سنة النشر: | 2024 |
| المجموعة: | University of Glasgow: Enlighten - Publications |
| الوصف: | Colorectal cancer (CRC) is the third most prevalent cancer worldwide with a high mortality rate (20–30%), especially due to metastasis to adjacent organs. Clinical responses to chemotherapy, radiation, targeted and immunotherapies are limited to a subset of patients making metastatic CRC (mCRC) difficult to treat. To understand the therapeutic modulation of immune response in mCRC, we have used a genetically engineered mouse model (GEMM), “KPN”, which resembles the human ‘CMS4’-like subtype. We show here that transforming growth factor (TGF-β1), secreted by KPN organoids, increases cancer cell proliferation, and inhibits splenocyte activation in vitro. TGF-β1 also inhibits activation of naive but not pre-activated T cells, suggesting differential effects on specific immune cells. In vivo, the inhibition of TGF-β inflames the KPN tumors, causing infiltration of T cells, monocytes and monocytic intermediates, while reducing neutrophils and epithelial cells. Co-inhibition of TGF-β and PD-L1 signaling further enhances cytotoxic CD8+T cells and upregulates innate immune response and interferon gene signatures. However, simultaneous upregulation of cancer-related metabolic genes correlated with limited control of tumor burden and/or progression despite combination treatment. Our study illustrates the importance of using GEMMs to predict better immunotherapies for mCRC. |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | text |
| اللغة: | English |
| العلاقة: | https://eprints.gla.ac.uk/322641/1/322641.pdfTest; Nair, R. , Lannagan, T. R.M., Jackstadt, R., Andrusaite, A. , Cole, J. , Boyne, C. , Nibbs, R. J.B. , Sansom, O. J. and Milling, S. (2024) Co-inhibition of TGF-β and PD-L1 pathways in a metastatic colorectal cancer mouse model triggers interferon responses, innate cells and T cells, alongside metabolic changes and tumor resistance. OncoImmunology , 13(1), 2330194. (doi:10.1080/2162402X.2024.2330194 ) |
| الإتاحة: | https://doi.org/10.1080/2162402X.2024.2330194Test https://eprints.gla.ac.uk/322641Test/ https://eprints.gla.ac.uk/322641/1/322641.pdfTest |
| حقوق: | cc_by_4 |
| رقم الانضمام: | edsbas.8E87FBBF |
| قاعدة البيانات: | BASE |
| الوصف غير متاح. |