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Reprogramming the immunological microenvironment through radiation and targeting Axl

Author

Listed:
  • Todd A. Aguilera

    (269 Campus Drive, Stanford University)

  • Marjan Rafat

    (269 Campus Drive, Stanford University)

  • Laura Castellini

    (269 Campus Drive, Stanford University)

  • Hussein Shehade

    (269 Campus Drive, Stanford University)

  • Mihalis S. Kariolis

    (269 Campus Drive, Stanford University)

  • Angela Bik-Yu Hui

    (Stanford Cancer Institute)

  • Henning Stehr

    (269 Campus Drive, Stanford University)

  • Rie von Eyben

    (269 Campus Drive, Stanford University)

  • Dadi Jiang

    (269 Campus Drive, Stanford University)

  • Lesley G. Ellies

    (University of California San Diego)

  • Albert C. Koong

    (269 Campus Drive, Stanford University
    Stanford Cancer Institute)

  • Maximilian Diehn

    (269 Campus Drive, Stanford University
    Stanford Cancer Institute)

  • Erinn B. Rankin

    (269 Campus Drive, Stanford University
    Stanford Cancer Institute)

  • Edward E. Graves

    (269 Campus Drive, Stanford University
    Stanford Cancer Institute)

  • Amato J. Giaccia

    (269 Campus Drive, Stanford University
    Stanford Cancer Institute)

Abstract

Increasing evidence suggests that ionizing radiation therapy (RT) in combination with checkpoint immunotherapy is highly effective in treating a subset of cancers. To better understand the limited responses to this combination we analysed the genetic, microenvironmental, and immune factors in tumours derived from a transgenic breast cancer model. We identified two tumours with similar growth characteristics but different RT responses primarily due to an antitumour immune response. The combination of RT and checkpoint immunotherapy resulted in cures in the responsive but not the unresponsive tumours. Profiling the tumours revealed that the Axl receptor tyrosine kinase is overexpressed in the unresponsive tumours, and Axl knockout resulted in slower growth and increased radiosensitivity. These changes were associated with a CD8+ T-cell response, which was improved in combination with checkpoint immunotherapy. These results suggest a novel role for Axl in suppressing antigen presentation through MHCI, and enhancing cytokine release, which promotes a suppressive myeloid microenvironment.

Suggested Citation

  • Todd A. Aguilera & Marjan Rafat & Laura Castellini & Hussein Shehade & Mihalis S. Kariolis & Angela Bik-Yu Hui & Henning Stehr & Rie von Eyben & Dadi Jiang & Lesley G. Ellies & Albert C. Koong & Maxim, 2016. "Reprogramming the immunological microenvironment through radiation and targeting Axl," Nature Communications, Nature, vol. 7(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms13898
    DOI: 10.1038/ncomms13898
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    Cited by:

    1. Thillai V. Sekar & Eslam A. Elghonaimy & Katy L. Swancutt & Sebastian Diegeler & Isaac Gonzalez & Cassandra Hamilton & Peter Q. Leung & Jens Meiler & Cristina E. Martina & Michael Whitney & Todd A. Ag, 2023. "Simultaneous selection of nanobodies for accessible epitopes on immune cells in the tumor microenvironment," Nature Communications, Nature, vol. 14(1), pages 1-20, December.

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