PIP4K Inhibition Shown to Restrict Tregs without Affecting Teffs

A team from the University of Southampton says it has found a way to restrict the activity of T-regulatory cells (Tregs). Detection and removal of cancer cells by the immune system is carried out in part by Teffector cells (Teffs), but how well Teff cells work in detecting and removing cancer cells is dictated by Tregs, which physically interact with the Teff cells and produce molecules that reduce the ability of the Teff cells to work properly.

"Tregs carry out an important function in the human body because without them, the immune system can run out of control and attack normal cells of the body,” explained study leader Nullin Divecha. “However, in cancer patients we need to give the Teff cells more freedom to carry out their job."

Molecules released by tumor cells compound the problem by attracting and accumulating Tregs, further reducing the activity and function of Teff cells. Mechanisms do exist to inhibit Treg cells, however as Treg and Teff cells are very similar, these generally also lead to inhibition of Teff cells.

In this new study, published in Proceedings of the National Academy of Sciences, the team showed that inhibition of PIP4K could be the answer to how to restrict Tregs without affecting Teffs. The research team isolated Tregs from healthy donors and used genetic technology to suppress the production of the PIP4K proteins. They observed that loss of PIP4Ks from Treg cells stopped them growing and responding to immune signals, which would therefore stop them from blocking the growth and function of Teff cells.

Importantly, the loss of the same enzymes in Teff cells did not limit their activity. "This was surprising because PIP4Ks are in both types of T cells in similar concentrations but our study shows that they seem to have a more important function for Tregs than Teffectors," said first author of the study Alessandro Poli.