Increased effect of two-fraction radiotherapy in conjunction with IDO1 inhibition in experimental glioblastoma
Ahlstedt, Jonatan LU
; Konradsson, Elise
LU
; Ceberg, Crister
LU
and Redebrandt, Henrietta Nittby
LU
(2020)
In PLoS ONE
15(5).
- Abstract
Objectives The aim of the study was to investigate therapeutic efficacy of single-or two-fraction radiotherapy in conjunction with IDO1-inhibition in a syngeneic rat glioblastoma model. IDO is known to cause immunosuppression through breakdown of tryptophan in the tumor microenvironment. Methods Gene expression analyses of IDO in glioblastoma were performed with data from publicly available datasets. Fractionation studies were done on animals to evaluate tumor size, immune cell infiltration of tumors and serum profile on day 18 after tumor inoculation. Survival analyses were done with animals carrying intracranial glioblastomas comparing twofraction radiotherapy+IDO1-inhibition to controls. IDO inhibition was achieved by administration... (More)
Objectives The aim of the study was to investigate therapeutic efficacy of single-or two-fraction radiotherapy in conjunction with IDO1-inhibition in a syngeneic rat glioblastoma model. IDO is known to cause immunosuppression through breakdown of tryptophan in the tumor microenvironment. Methods Gene expression analyses of IDO in glioblastoma were performed with data from publicly available datasets. Fractionation studies were done on animals to evaluate tumor size, immune cell infiltration of tumors and serum profile on day 18 after tumor inoculation. Survival analyses were done with animals carrying intracranial glioblastomas comparing twofraction radiotherapy+IDO1-inhibition to controls. IDO inhibition was achieved by administration of 1-methyl tryptophan (1-MT), and radiotherapy (RT) was delivered in doses of 8Gy. Results The expression of IDO1 was increased on gene level in glioblastoma stem cells. Tumor size was significantly reduced in animals treated with 1-MT+RTx 2 (both long and short intervals, i.e. 7 and 4 days between the treatments) as compared to control animals, animals treated with only 1-MT or animals treated with 1-MT+RTx1. Serum levels of IL-1A were significantly altered in all treated animals as compared to control animals. Survival was significantly increased in the animals treated with 1-MT+RTx2 (7-day interval) compared to control animals. Conclusions Addition of two-fraction RT to IDO1 inhibition with 1-MT significantly reduced tumor size in animals with glioblastoma. Survival was significantly increased in animals treated with twofractioned RT+1-MT as compared to untreated controls increased significantly. Advances in knowledge The currently used combination of only two fractions of radiotherapy and immune therapy is a promising area of research, increasing efficacy compared to single fraction irradiation, while potentially lowering radiation side effects compared to radiation in current clinical practice.
(Less)
- author
- Ahlstedt, Jonatan
LU
; Konradsson, Elise
LU
; Ceberg, Crister
LU
and Redebrandt, Henrietta Nittby
LU
- organization
- publishing date
- 2020-05
- type
- Contribution to journal
- publication status
- published
- subject
- in
- PLoS ONE
- volume
- 15
- issue
- 5
- article number
- e0233617
- publisher
- Public Library of Science (PLoS)
- external identifiers
-
- scopus:85085904228
- pmid:32469935
- ISSN
- 1932-6203
- DOI
- 10.1371/journal.pone.0233617
- language
- English
- LU publication?
- yes
- id
- 21421938-64ae-44ac-9c8f-814c879f3b79
- date added to LUP
- 2021-01-14 13:52:57
- date last changed
- 2024-06-13 05:11:18
@article{21421938-64ae-44ac-9c8f-814c879f3b79,
abstract = {{<p>Objectives The aim of the study was to investigate therapeutic efficacy of single-or two-fraction radiotherapy in conjunction with IDO1-inhibition in a syngeneic rat glioblastoma model. IDO is known to cause immunosuppression through breakdown of tryptophan in the tumor microenvironment. Methods Gene expression analyses of IDO in glioblastoma were performed with data from publicly available datasets. Fractionation studies were done on animals to evaluate tumor size, immune cell infiltration of tumors and serum profile on day 18 after tumor inoculation. Survival analyses were done with animals carrying intracranial glioblastomas comparing twofraction radiotherapy+IDO1-inhibition to controls. IDO inhibition was achieved by administration of 1-methyl tryptophan (1-MT), and radiotherapy (RT) was delivered in doses of 8Gy. Results The expression of IDO1 was increased on gene level in glioblastoma stem cells. Tumor size was significantly reduced in animals treated with 1-MT+RTx 2 (both long and short intervals, i.e. 7 and 4 days between the treatments) as compared to control animals, animals treated with only 1-MT or animals treated with 1-MT+RTx1. Serum levels of IL-1A were significantly altered in all treated animals as compared to control animals. Survival was significantly increased in the animals treated with 1-MT+RTx2 (7-day interval) compared to control animals. Conclusions Addition of two-fraction RT to IDO1 inhibition with 1-MT significantly reduced tumor size in animals with glioblastoma. Survival was significantly increased in animals treated with twofractioned RT+1-MT as compared to untreated controls increased significantly. Advances in knowledge The currently used combination of only two fractions of radiotherapy and immune therapy is a promising area of research, increasing efficacy compared to single fraction irradiation, while potentially lowering radiation side effects compared to radiation in current clinical practice.</p>}},
author = {{Ahlstedt, Jonatan and Konradsson, Elise and Ceberg, Crister and Redebrandt, Henrietta Nittby}},
issn = {{1932-6203}},
language = {{eng}},
number = {{5}},
publisher = {{Public Library of Science (PLoS)}},
series = {{PLoS ONE}},
title = {{Increased effect of two-fraction radiotherapy in conjunction with IDO1 inhibition in experimental glioblastoma}},
url = {{http://dx.doi.org/10.1371/journal.pone.0233617}},
doi = {{10.1371/journal.pone.0233617}},
volume = {{15}},
year = {{2020}},
}