Abstract
Backgrounds
Wilms’ tumor gene 1 (WT1) peptide vaccine and anti-programmed cell death-1 (PD-1) antibody are expected as immunotherapies to improve the clinical outcome of glioblastoma. The aims of this study were to clarify how each immunotherapy affect tumor-infiltrating immune cells (TIIs) and to determine whether the combination of these two therapies could synergistically work.
Methods
Mice were transplanted with WT1 and programed cell death-ligand 1 (PD-L1) doubly expressing glioblastoma cells into brain followed by treatment with WT1 peptide vaccine, anti-PD-1 antibody, or the combination of the two, and survival of each therapy was compared. CD45 + cells were positively selected as TIIs from the brains with tumors, and TIIs were compared between WT1 peptide vaccine and anti-PD-1 antibody therapies.
Results
Most mice seemed to be cured by the combination therapy with WT1 peptide vaccine and anti-PD-1 antibody, which was much better survival than each monotherapy. A large number of CD4 + T cells, CD8 + T cells, NK cells including WT1-specific CD8 + and CD4 + T cells infiltrated into the glioblastoma in WT1 peptide vaccine-treated mice. On the other hand, the number of TIIs did not increase, but instead PD-1 molecule expression was decreased on the majority of the tumor-infiltrating CD8 + T cells in the anti-PD-1 antibody-treated mice.
Conclusion
Our results clearly demonstrated that WT1 peptide vaccine and anti-PD-1 antibody therapies worked in the different steps of cancer-immunity cycle and that the combination of the two therapies could work synergistically against glioblastoma.
Sensitivity Assessment of Wilms Tumor Gene (WT1) Expression in Glioblastoma using qPCR and Immunohistochemistry and its Association with IDH1 Mutation and Recurrence Interval