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Long-term anti-tumor effects following both conventional radiotherapy and FLASH in fully immunocompetent animals with glioblastoma

Liljedahl, Emma LU ; Konradsson, Elise LU ; Gustafsson, Emma LU ; Jonsson, Karolina Förnvik LU orcid ; Olofsson, Jill K ; Ceberg, Crister LU orcid and Redebrandt, Henrietta Nittby LU (2022) In Scientific Reports 12(1). p.12285-12285
Abstract

Radiotherapy can induce an immunological response. One limiting factor is side effects on normal tissue. Using FLASH radiotherapy, side effects could possibly be reduced. The efficacy of FLASH in relation to conventional radiotherapy (CONV-RT) has not been extensively explored in fully immunocompetent animals. Fully immunocompetent Fischer 344 rats were inoculated with NS1 glioblastoma cells subcutaneously or intracranially. Radiotherapy was delivered with FLASH or CONV-RT at 8 Gy × 2 (subcutaneous tumors) and 12.5 Gy × 2 (intracranial tumors). Cured animals were re-challenged in order to explore long-term anti-tumor immunity. Serum analytes and gene expression were explored. The majority of animals with subcutaneous tumors were cured... (More)

Radiotherapy can induce an immunological response. One limiting factor is side effects on normal tissue. Using FLASH radiotherapy, side effects could possibly be reduced. The efficacy of FLASH in relation to conventional radiotherapy (CONV-RT) has not been extensively explored in fully immunocompetent animals. Fully immunocompetent Fischer 344 rats were inoculated with NS1 glioblastoma cells subcutaneously or intracranially. Radiotherapy was delivered with FLASH or CONV-RT at 8 Gy × 2 (subcutaneous tumors) and 12.5 Gy × 2 (intracranial tumors). Cured animals were re-challenged in order to explore long-term anti-tumor immunity. Serum analytes and gene expression were explored. The majority of animals with subcutaneous tumors were cured when treated with FLASH or CONV-RT at 8 Gy × 2. Cured animals could reject tumor re-challenge. TIMP-1 in serum was reduced in animals treated with FLASH 8 Gy × 2 compared to control animals. Animals with intracranial tumors survived longer when treated with FLASH or CONV-RT at 12.5 Gy × 2, but cure was not reached. CONV-RT and FLASH were equally effective in fully immunocompetent animals with glioblastoma. Radiotherapy was highly efficient in the subcutaneous setting, leading to cure and long-term immunity in the majority of the animals.

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author
; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Animals, Brain Neoplasms/etiology, Glioblastoma/etiology, Radiotherapy/adverse effects, Radiotherapy Dosage, Rats
in
Scientific Reports
volume
12
issue
1
pages
12285 - 12285
publisher
Nature Publishing Group
external identifiers
  • pmid:35853933
  • scopus:85134411190
ISSN
2045-2322
DOI
10.1038/s41598-022-16612-6
language
English
LU publication?
yes
additional info
© 2022. The Author(s).
id
f08f4b55-089d-4566-9a36-fddc37223951
date added to LUP
2022-09-06 21:33:33
date last changed
2024-06-27 20:30:08
@article{f08f4b55-089d-4566-9a36-fddc37223951,
  abstract     = {{<p>Radiotherapy can induce an immunological response. One limiting factor is side effects on normal tissue. Using FLASH radiotherapy, side effects could possibly be reduced. The efficacy of FLASH in relation to conventional radiotherapy (CONV-RT) has not been extensively explored in fully immunocompetent animals. Fully immunocompetent Fischer 344 rats were inoculated with NS1 glioblastoma cells subcutaneously or intracranially. Radiotherapy was delivered with FLASH or CONV-RT at 8 Gy × 2 (subcutaneous tumors) and 12.5 Gy × 2 (intracranial tumors). Cured animals were re-challenged in order to explore long-term anti-tumor immunity. Serum analytes and gene expression were explored. The majority of animals with subcutaneous tumors were cured when treated with FLASH or CONV-RT at 8 Gy × 2. Cured animals could reject tumor re-challenge. TIMP-1 in serum was reduced in animals treated with FLASH 8 Gy × 2 compared to control animals. Animals with intracranial tumors survived longer when treated with FLASH or CONV-RT at 12.5 Gy × 2, but cure was not reached. CONV-RT and FLASH were equally effective in fully immunocompetent animals with glioblastoma. Radiotherapy was highly efficient in the subcutaneous setting, leading to cure and long-term immunity in the majority of the animals.</p>}},
  author       = {{Liljedahl, Emma and Konradsson, Elise and Gustafsson, Emma and Jonsson, Karolina Förnvik and Olofsson, Jill K and Ceberg, Crister and Redebrandt, Henrietta Nittby}},
  issn         = {{2045-2322}},
  keywords     = {{Animals; Brain Neoplasms/etiology; Glioblastoma/etiology; Radiotherapy/adverse effects; Radiotherapy Dosage; Rats}},
  language     = {{eng}},
  month        = {{07}},
  number       = {{1}},
  pages        = {{12285--12285}},
  publisher    = {{Nature Publishing Group}},
  series       = {{Scientific Reports}},
  title        = {{Long-term anti-tumor effects following both conventional radiotherapy and FLASH in fully immunocompetent animals with glioblastoma}},
  url          = {{http://dx.doi.org/10.1038/s41598-022-16612-6}},
  doi          = {{10.1038/s41598-022-16612-6}},
  volume       = {{12}},
  year         = {{2022}},
}