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Effect of Blockade of Indoleamine 2, 3-dioxygenase in Conjunction with Single Fraction Irradiation in Rat Glioma

AHLSTEDT, JONATAN LU ; Förnvik, Karolina LU ; Ceberg, Crister LU and Nittby, Henrietta LU (2015) In Jacobs journal of radiation oncology 2(3).
Abstract
Glioblastoma (GBM), or WHO Astrocytoma grade IV, is the most common primary brain tumour in adults. GBM is shown to
escape host immune surveillance through many paths, of which expression of indoleamine 2,3-dioxygenase (IDO), leading
to induction and accumulation of regulatory T-cells in the tumour microenvironment, has been shown to be of importance.
1-Methyl tryptophan (1-MT) is an inhibitor of IDO that has been shown to have a positive effect on survival in experimental
models of GBM. In this study, we evaluate the effect of combined single-fraction irradiation of 8 Gy with 1-MT treatment in
Fischer rats carrying the... (More)
Glioblastoma (GBM), or WHO Astrocytoma grade IV, is the most common primary brain tumour in adults. GBM is shown to
escape host immune surveillance through many paths, of which expression of indoleamine 2,3-dioxygenase (IDO), leading
to induction and accumulation of regulatory T-cells in the tumour microenvironment, has been shown to be of importance.
1-Methyl tryptophan (1-MT) is an inhibitor of IDO that has been shown to have a positive effect on survival in experimental
models of GBM. In this study, we evaluate the effect of combined single-fraction irradiation of 8 Gy with 1-MT treatment in
Fischer rats carrying the RG2 glioma model. We also investigate expression of IDO in the RG2 model before and after irradiation.
Thirty-three Fischer 344 rats received intracranial inoculations of RG2 tumour cells, and were treated with either intraperito-
neal 1-MT, 8 Gy single-fraction radiotherapy, or a combination of the two. Survival in the combined treatment group (29 days ±
0.75) was significantly better than controls (20 ± 0.99, p=0.015) and radiation only (17 ± 2.75, p=0.014). Survival was also better
with combined treatment compared to 1-MT only but the difference was non-significant (18 ± 0.28, p=0.215).
Our results add to the growing base of evidence suggesting 1-methyl-tryptophan is an attractive candidate for clinical investi-
gation in patients carrying highly malignant astrocytoma, especially in combination with radiation treatment, even in singular
fraction settings. (Less)
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Jacobs journal of radiation oncology
volume
2
issue
3
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2376-9424
language
English
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yes
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20d56f4e-f68e-452e-b650-57586d9f849e
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date added to LUP
2016-11-23 08:28:23
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2017-08-02 10:01:51
@article{20d56f4e-f68e-452e-b650-57586d9f849e,
  abstract     = {Glioblastoma  (GBM),  or  WHO  Astrocytoma  grade  IV,  is  the  most  common  primary  brain  tumour  in  adults.  GBM  is  shown  to  <br/>escape  host  immune  surveillance  through  many  paths,  of  which  expression  of  indoleamine  2,3-dioxygenase  (IDO),  leading  <br/>to  induction  and  accumulation  of  regulatory  T-cells  in  the  tumour  microenvironment,  has  been  shown  to  be  of  importance.  <br/>1-Methyl  tryptophan  (1-MT)  is  an  inhibitor  of  IDO  that  has  been  shown  to  have  a  positive  effect  on  survival  in  experimental  <br/>models  of  GBM.  In  this  study,  we  evaluate  the  effect  of  combined  single-fraction  irradiation  of  8  Gy  with  1-MT  treatment  in  <br/>Fischer rats carrying the RG2 glioma model. We also investigate expression of IDO in the RG2 model before and after irradiation. <br/>Thirty-three Fischer 344 rats received intracranial inoculations of RG2 tumour cells, and were treated with either intraperito-<br/>neal 1-MT, 8 Gy single-fraction radiotherapy, or a combination of the two. Survival in the combined treatment group (29 days ± <br/>0.75) was significantly better than controls (20 ± 0.99, p=0.015) and radiation only (17 ± 2.75, p=0.014). Survival was also better <br/>with combined treatment compared to 1-MT only but the difference was non-significant (18 ± 0.28, p=0.215).<br/>Our results add to the growing base of evidence suggesting 1-methyl-tryptophan is an attractive candidate for clinical investi-<br/>gation in patients carrying highly malignant astrocytoma, especially in combination with radiation treatment, even in singular <br/>fraction settings.},
  articleno    = {022},
  author       = {AHLSTEDT, JONATAN and Förnvik, Karolina and Ceberg, Crister and Nittby, Henrietta},
  issn         = {2376-9424},
  language     = {eng},
  number       = {3},
  series       = {Jacobs journal of radiation oncology},
  title        = {Effect of Blockade of Indoleamine 2, 3-dioxygenase in Conjunction with Single  Fraction Irradiation in Rat Glioma},
  volume       = {2},
  year         = {2015},
}