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Harnessing Tumor Immune Ecosystem Dynamics to Personalize Radiation Therapy
66 Pages Posted: 7 May 2020 Publication Status: Review Complete
More...Abstract
Radiotherapy is a pillar of cancer care and augments the response to immunotherapies. However, little is known regarding the relationships between the tumor immune ecosystem (TIES) and intrinsic radiosensitivity. A pressing question in oncology is how to optimize radiotherapy to improve patient responses to immune therapies. To address this, we profiled 10,469 primary tumors for metrics of radiosensitivity and immune cell infiltrate (ICI), and applied a new integrated in silico model that mimics the dynamic relationships between tumor growth, ICI flux and radiation response. We validated this model in 10,469 primary tumors and a separate cohort of 59 lung cancer patients treated with radiotherapy. These analyses explain radiation response based on its effect on the TIES and quantifies the likelihood that radiation can promote a shift to anti-tumor immunity. Dynamic modeling of the relationship between tumor radiosensitivity and the TIES may provide opportunity to personalize combined radiation and immunotherapy approaches.
Keywords: Radiation therapy, Radiosensitivity, tumor immune microenvironment, mathematical models, genomic models, Radiation Oncology, personalized medicine, gene expression
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