PT  - JOURNAL ARTICLE
AU  - G. Daniel Grass
AU  - Juan C.L. Alfonso
AU  - Eric Welsh
AU  - Kamran A. Ahmed
AU  - Jamie K. Teer
AU  - Louis B. Harrison
AU  - John L. Cleveland
AU  - James J. Mulé
AU  - Steven A. Eschrich
AU  - Heiko Enderling
AU  - Javier F. Torres-Roca
TI  - Harnessing tumor immune ecosystem dynamics to personalize radiotherapy
AID  - 10.1101/2020.02.11.944512
DP  - 2020 Jan 01
TA  - bioRxiv
PG  - 2020.02.11.944512
4099  - http://biorxiv.org/content/early/2020/02/12/2020.02.11.944512.short
4100  - http://biorxiv.org/content/early/2020/02/12/2020.02.11.944512.full
AB  - 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, and a pressing question in oncology is how to optimize radiotherapy to improve patient responses to immune therapies. To address this challenge, we profiled over 10,000 primary tumors for their 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 the response to radiation. We then validated this model with 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.