Immunotherapy represents an exciting advance in cancer treatment that harnesses the immune system to seek and destroy cancer cells.

The programmed death 1 (PD-1) pathway dampens immune responses to tumour cells, and several clinical trials have shown favourable outcomes by targeting PD-1 or its ligand PD-1L.

In this issue of JCI Insight, David Hafler and colleagues at Yale University and Massachusetts Institute of Technology examined PD-1-expressing regulatory T cells in glioblastoma multiforme, an extremely aggressive form of brain cancer.

Regulatory T cells normally constrain immune responses and keep other types of T cells from mounting hyper-aggressive responses.

Although anti-PD1 therapy is generally thought to promote conventional T cell activity, the Hafler team now reports that PD-1 expression on regulatory T cells from the tumours of glioblastoma multiforme patients correlates with regulatory T cell dysfunction.

They also found that glioblastoma multiforme patients treated with a PD-1 blocking antibody had a higher proportion of dysfunctional regulatory T cells.

These observations suggest the possibility that PD-1 targeting therapies could work, in part, by driving further regulatory T cell dysfunction. Future studies will be needed to more fully understand the contribution of this pathway to anti-tumor effects.

"Anti-PD-1 therapy may work by destabilizing a crucial pathway for the function and de novo induction of Tregs." says Hafler. "It can be speculated that Tregs could directly promote tumour proliferation through production of oncogenic growth factors rather than by suppression of the antitumoral response."

Source: JCI Insight