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

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.