Synchrotron microbeam radiotherapy evokes a different early tumor immunomodulatory response to conventional radiotherapy in EMT6.5 mammary tumors

Yang Y 1 , Swierczak A 2 , Ibahim M 3 , Paiva P 1 , Cann L 1 , Stevenson AW 4 Show all authors , Crosbie JC 5 , Anderson RL 6 , Rogers PAW 1

Affiliations 

  • 1 Department of Obstetrics & Gynaecology, University of Melbourne, Royal Women's Hospital, Parkville, Australia
  • 2 MRC Centre for Reproductive Health, Queen's Medical Research Institute, The University of Edinburgh, UK
  • 3 Department of Obstetrics & Gynaecology, University of Melbourne, Royal Women's Hospital, Parkville, Australia; Faculty of Medicine, Universiti Teknologi MARA, Sungai Buloh Campus, Jalan Hospital, Selangor, Malaysia
  • 4 The Imaging and Medical Beamline, Australian Synchrotron, Clayton, Australia; CSIRO Materials Science & Engineering, Clayton, Australia
  • 5 Department of Obstetrics & Gynaecology, University of Melbourne, Royal Women's Hospital, Parkville, Australia; School of Science, RMIT University, Melbourne, Australia
  • 6 Sir Peter MacCallum Department of Oncology, The University of Melbourne, Australia; Olivia Newton-John Cancer Research Institute, Heidelberg, Australia; School of Cancer Medicine, La Trobe University, Australia. Electronic address: robin.anderson@onjcri.org.au
Radiother Oncol, 2019 04;133:93-99.
PMID: 30935588 DOI: 10.1016/j.radonc.2019.01.006

Abstract

BACKGROUND: Synchrotron microbeam radiation therapy (MRT) is a new, evolving form of radiotherapy that has potential for clinical application. Several studies have shown in preclinical models that synchrotron MRT achieves equivalent tumor control to conventional radiotherapy (CRT) but with significantly reduced normal tissue damage.

METHODS: To explore differences between these two modalities, we assessed the immune cell infiltrate into EMT6.5 mammary tumors after CRT and MRT.

RESULTS: CRT induced marked increases in tumor-associated macrophages and neutrophils while there were no increases in these populations following MRT. In contrast, there were higher numbers of T cells in the MRT treated tumors. There were also increased levels of CCL2 by immunohistochemistry in tumors subjected to CRT, but not to MRT. Conversely, we found that MRT induced higher levels of pro-inflammatory genes in tumors than CRT.

CONCLUSION: Our data are the first to demonstrate substantial differences in macrophage, neutrophil and T cell numbers in tumors following MRT versus CRT, providing support for the concept that MRT evokes a different immunomodulatory response in tumors compared to CRT.

* Title and MeSH Headings from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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