New research has identified a potential treatment that could improve the
human immune system’s ability to search out and destroy cancer cells within
the body. Scientists have identified a way to restrict the activity of a
group of cells that regulate the immune system, which in turn can unleash
other immune cells to attack tumours in cancer patients.
“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.” Explained Nullin Divecha, Professor of Cell
Signalling at the University of Southampton who led the study. “However,
cancer cells can generate a microenvironment within the tumour that stops
the immune system from working thereby limiting the general use and success
of immunotherapy,” he continued.
Detection and removal of cancer cells by the immune system is carried out in
part by a group of cells called Teffector cells (Teffs). How well Teff cells
work in detecting and removing cancer cells is in part dictated by other T
cells called T-regulatory cells, or Tregs for short. Tregs physically
interact with the Teff cells and produce molecules which reduce the ability
of the Teff cells to work properly.
Prof Divecha added, “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.”
Molecules released by tumour 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 the journal Proceedings of the National
Academy of Sciences of the United States of America, scientists from the
University of Southampton and the National Institute of Molecular Genetics
in Milan showed that inhibition of a family of enzymes in cells called 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 Dr. Alessandro Poli who carried
out the experimental research.
Inhibition of PIP4K as a potential therapeutic for patients requires the
development of inhibitory molecules. “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 tumour cells.”
Reference:
PIP4Ks impact on PI3K, FOXP3 and UHRF1 signaling and modulate human
regulatory T-cell proliferation and immunosuppressive activity 26 July 2021, Proceedings of the National Academy of Sciences.
DOI: https://doi.org/10.1073/pnas.2010053118