Transient regulatory T cell ablation deters oncogene-driven breast cancer and enhances radiotherapy Journal Article
| Authors: | Bos, P. D.; Plitas, G.; Rudra, D.; Lee, S. Y.; Rudensky, A. Y. |
| Article Title: | Transient regulatory T cell ablation deters oncogene-driven breast cancer and enhances radiotherapy |
| Abstract: | Rational combinatorial therapeutic strategies have proven beneficial for the management of cancer. Recent success of checkpoint blockade in highly immunogenic tumors has renewed interest in immunotherapy. Regulatory T (T reg) cells densely populate solid tumors, which may promote progression through suppressing anti-tumor immune responses. We investigated the role of T reg cells in murine mammary carcinogenesis using an orthotopic, polyoma middle-T antigen-driven model in Foxp3DTR knockin mice. T reg cell ablation resulted in significant determent of primary and metastatic tumor progression. Importantly, short-term ablation of T reg cells in advanced spontaneous tumors led to extensive apoptotic tumor cell death. This anti-tumor activity was dependent on IFN-γ and CD4+ T cells but not on NK or CD8+ T cells. Combination of T reg cell ablation with CTLA-4 or PD-1/PD-L1 blockade did not affect tumor growth or improve the therapeutic effect attained by T reg cell ablation alone. However, T reg cell targeting jointly with tumor irradiation significantly reduced tumor burden and improved overall survival. Together, our results demonstrate a major tumor-promoting role of T reg cells in an autochthonous model of tumorigenesis, and they reveal the potential therapeutic value of combining transient T reg cell ablation with radiotherapy for the management of poorly immunogenic, aggressive malignancies. © 2013 Bos et al. |
| Journal Title: | Journal of Experimental Medicine |
| Volume: | 210 |
| Issue: | 11 |
| ISSN: | 0022-1007 |
| Publisher: | Rockefeller University Press |
| Date Published: | 2013-10-01 |
| Start Page: | 2435 |
| End Page: | 2466 |
| Language: | English |
| DOI: | 10.1084/jem.20130762 |
| PROVIDER: | scopus |
| PMCID: | PMC3804934 |
| PUBMED: | 24127486 |
| DOI/URL: | |
| Notes: | --- - "Export Date: 2 December 2013" - "CODEN: JEMEA" - "Source: Scopus" |
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