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Harnessing tumor immune ecosystem dynamics to personalize radiotherapy

G. Daniel Grass, Juan C.L. Alfonso, Eric Welsh, Kamran A. Ahmed, Jamie K. Teer, Louis B. Harrison, John L. Cleveland, James J. Mulé, Steven A. Eschrich, Heiko Enderling, Javier F. Torres-Roca
doi: https://doi.org/10.1101/2020.02.11.944512
G. Daniel Grass
1Departments of Radiation Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa FL, USA
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Juan C.L. Alfonso
6Departments of Braunschweig Integrated Centre of Systems Biology, Helmholtz Centre for Infection Research
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Eric Welsh
2Departments of Biostatistics and Bioinformatics, H. Lee Moffitt Cancer Center and Research Institute, Tampa FL, USA
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Kamran A. Ahmed
1Departments of Radiation Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa FL, USA
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Jamie K. Teer
2Departments of Biostatistics and Bioinformatics, H. Lee Moffitt Cancer Center and Research Institute, Tampa FL, USA
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Louis B. Harrison
1Departments of Radiation Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa FL, USA
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John L. Cleveland
3Departments of Tumor Biology, H. Lee Moffitt Cancer Center and Research Institute, Tampa FL, USA
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James J. Mulé
4Departments of Immunology, H. Lee Moffitt Cancer Center and Research Institute, Tampa FL, USA
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Steven A. Eschrich
2Departments of Biostatistics and Bioinformatics, H. Lee Moffitt Cancer Center and Research Institute, Tampa FL, USA
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Heiko Enderling
1Departments of Radiation Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa FL, USA
5Departments of Integrated Mathematical Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa FL, USA
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  • For correspondence: Javier.TorresRoca@moffitt.org Heiko.Enderling@moffitt.org
Javier F. Torres-Roca
1Departments of Radiation Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa FL, USA
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  • For correspondence: Javier.TorresRoca@moffitt.org Heiko.Enderling@moffitt.org
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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, 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.

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  • ↵** co-senior authors

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted February 12, 2020.
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Harnessing tumor immune ecosystem dynamics to personalize radiotherapy
G. Daniel Grass, Juan C.L. Alfonso, Eric Welsh, Kamran A. Ahmed, Jamie K. Teer, Louis B. Harrison, John L. Cleveland, James J. Mulé, Steven A. Eschrich, Heiko Enderling, Javier F. Torres-Roca
bioRxiv 2020.02.11.944512; doi: https://doi.org/10.1101/2020.02.11.944512
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Harnessing tumor immune ecosystem dynamics to personalize radiotherapy
G. Daniel Grass, Juan C.L. Alfonso, Eric Welsh, Kamran A. Ahmed, Jamie K. Teer, Louis B. Harrison, John L. Cleveland, James J. Mulé, Steven A. Eschrich, Heiko Enderling, Javier F. Torres-Roca
bioRxiv 2020.02.11.944512; doi: https://doi.org/10.1101/2020.02.11.944512

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