Re-purposing the pro-senescence properties of doxorubicin to introduce immunotherapy in breast cancer brain metastasis
dc.contributor.author | Uceda-Castro, R. | |
dc.contributor.author | Margarido, A. S. | |
dc.contributor.author | Cornet, L. | |
dc.contributor.author | Vegna, S. | |
dc.contributor.author | Hahn, K. | |
dc.contributor.author | Song, J. Y. | |
dc.contributor.author | Putavet, D. A. | |
dc.contributor.author | van Geldorp, M. | |
dc.contributor.author | Çitirikkaya, C. H. | |
dc.contributor.author | de Keizer, P. L. J. | |
dc.contributor.author | Ter Beek, L. C. | |
dc.contributor.author | Borst, Gerben R | |
dc.contributor.author | Akkari, L. | |
dc.contributor.author | van Tellingen, O. | |
dc.contributor.author | Broekman, M. L. D. | |
dc.contributor.author | Vennin, C. | |
dc.contributor.author | van Rheenen, J. | |
dc.date.accessioned | 2023-01-16T14:12:42Z | |
dc.date.available | 2023-01-16T14:12:42Z | |
dc.date.issued | 2022 | en |
dc.identifier.citation | Uceda-Castro R, Margarido AS, Cornet L, Vegna S, Hahn K, Song JY, et al. Re-purposing the pro-senescence properties of doxorubicin to introduce immunotherapy in breast cancer brain metastasis. Cell reports Medicine. 2022 Nov 15;3(11):100821. PubMed PMID: 36384097. Pubmed Central PMCID: PMC9729880. Epub 2022/11/18. eng. | en |
dc.identifier.pmid | 36384097 | en |
dc.identifier.doi | 10.1016/j.xcrm.2022.100821 | en |
dc.identifier.uri | http://hdl.handle.net/10541/625852 | |
dc.description.abstract | An increasing number of breast cancer patients develop brain metastases (BM). Standard-of-care treatments are largely inefficient, and breast cancer brain metastasis (BCBM) patients are considered untreatable. Immunotherapies are not successfully employed in BCBM, in part because breast cancer is a "cold" tumor and also because the brain tissue has a unique immune landscape. Here, we generate and characterize immunocompetent models of BCBM derived from PyMT and Neu mammary tumors to test how harnessing the pro-senescence properties of doxorubicin can be used to prime the specific immune BCBM microenvironment. We reveal that BCBM senescent cells, induced by doxorubicin, trigger the recruitment of PD1-expressing T cells to the brain. Importantly, we demonstrate that induction of senescence with doxorubicin improves the efficacy of immunotherapy with anti-PD1 in BCBM in a CD8 T cell-dependent manner, thereby providing an optimized strategy to introduce immune-based treatments in this lethal disease. In addition, our BCBM models can be used for pre-clinical testing of other therapeutic strategies in the future. | en |
dc.language.iso | en | en |
dc.relation.url | https://dx.doi.org/10.1016/j.xcrm.2022.100821 | en |
dc.title | Re-purposing the pro-senescence properties of doxorubicin to introduce immunotherapy in breast cancer brain metastasis | en |
dc.type | Article | en |
dc.contributor.department | Division of Molecular Pathology, Oncode Institute, The Netherlands Cancer Institute, 1066 Amsterdam, North Holland, the Netherlands | en |
dc.identifier.journal | Cell Reports. Medicine | en |
dc.description.note | en] | |
refterms.dateFOA | 2023-01-17T09:27:17Z |