SOUTHAMPTON, United Kingdom — Scientists at the University of Southampton have identified a potentially groundbreaking new treatment that may improve the human immune system’s ability to seek out and destroy cancer cells. The approach is quite strategic: By restricting a group of cells known to regulate and impede immune responses, the treatment frees up a bevy of other immune cells that then go on to attack tumors and cancer cells.
“A patient’s immune system is more than able to detect and remove cancer cells and immunotherapy has recently emerged as a novel therapy for many different types of cancers.” explains study leader Nullin Divecha, Professor of Cell Signaling at the University of Southampton, in a university release. “However, cancer cells can generate a microenvironment within the tumor that stops the immune system from working thereby limiting the general use and success of immunotherapy.”
Researchers say Teffector cells (Teffs) in the immune system detect and kill cancer cells. However, just like so much else in the human body, it isn’t as simple as it sounds. The efficiency of Teffs partially depends on another type of immune cell called T-regulatory cells (Tregs). Tregs interact with Teffs and impede the Teff cells from performing their job to the best of their cellular ability.
“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. However, in cancer patients we need to give the Teff cells more freedom to carry out their job,” Prof. Divecha adds.
Stopping enzymes that hinder cancer-fighting cells
Tumor cell-released molecules add to the problem because they attract Tregs, making it ever harder for Teffs to do their cancer-killing job. While there are avenues of inhibiting Treg cells, Treg and Teff cells are very similar, meaning such efforts usually lead to the disruption of both immune cell varieties.
On a positive note, this new research discovered that inhibiting a family of enzymes in cells called PIP4K may successfully restrict Tregs without doing the same to Teffs.
First, the team isolated Tregs from healthy donors before using genetic technology to suppress PIP4K protein production. When the Treg cells lost their PIP4Ks, they stopped growing, responding to immune distress, and messing with the Teff cells. Importantly, this process didn’t effect the Teff cells at all.
“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,” says study co-author Dr. Alessandro Poli. “Towards this end we show that treatment with a drug like inhibitor of PIP4K could enable the immune system to function more strongly and be better equipped to destroy tumor cells.”
The findings appear in the journal Proceedings of the National Academy of Sciences.