Glioblastoma has an extremely poor prognosis, and there is a critical need for new therapies to treat the disease.
Immunotherapy helps the immune system destroy cancer cells, and recent clinical evaluation of an immune cell-based vaccine has shown some benefits in early stage trials.
Unfortunately, the response to this vaccine varies greatly amongst patients.
In this issue of JCI Insight, Robert Prins of UCLA and colleagues tested whether they could improve the efficacy of an antitumour vaccine in a murine glioblastoma model by simultaneously administering therapeutic antibodies that turn off so-called immune checkpoint molecules, known as PD-1 and PD-L1, which attenuate immune responses.
Using mice with established tumours, the research team showed that immune checkpoint blockade in combination with an antitumour vaccine improved survival and promoted infiltration of immune cells into the tumours.
"We demonstrated drastically improved survival in the in vivo setting following both treatments." the authors report. "With this study, we also demonstrated the necessity of a vaccine-generated TIL population in order for the PD-1 pathway to be able to exert an effect within GBM tumours."
These results of this study suggest that PD-1 and PD-L1 may help tumours become resistant to antitumour vaccines.
Moreover, this study supports testing of such therapeutic combinations in clinical trials.
"Although there is probably a broad spectrum of tumour environment–mediated adaptive inhibition, PD-1 is a likely dominant regulatory mechanism in vaccine-induced immune suppression in our model" the authors conclude. "Future studies are needed to better understand what is likely a heterogeneous array of mechanisms utilised to prevent antitumour activity. The interplay of these mechanisms may provide the key to successfully treating GBM using endogenous immune mechanisms."
Source: JCI Insight