New Nature Communications Paper – Improving The Effectiveness Of Cancer Therapy ICI By Inhibiting PARP14

by | Sep 26, 2023 | News, Publications | 0 comments

A study by Dr Adam Hurlstone and colleagues from the Lydia Becker Institute addressing how to improve the effectiveness of a class of cancer therapy called immune checkpoint inhibitors (ICI) has been published in the September issue of the prestigious journal Nature Communications

ICI work by activating T cells which are a part of our immune system that are capable of destroying cancer cells. However, there appears to be feedback mechanisms that limit how long and how well these ICI work. Active T cells secrete a hormone-like protein called interferon gamma (IFNg). While IFNg is needed to stimulate immune cells, when it is present for too long it does the opposite and inhibits immune responses.

Dr Hurlstone explained:

We looked at how too long exposure to IFNg inhibits immune responses. We found that an enzyme called PARP14 becomes too active in cancer cells. Also PARP14 made by T cells pushes immune responses away from those driven by T cells towards those driven by antibodies which are less effective at destroying cancer cells.


By inhibiting PARP14 we could restore sensitivity to ICI in cancer models made by injecting cancer cells into mice which had developed resistance because of too long exposure to IFNg.

The reagent used in the study to inhibit PARP14 is a drug made by Ribon Therapeutics and they are already clinically testing a very similar PARP14 drug for its ability to suppress asthma.

Dr Hurlstone believes it’s possible that a PARP14 drug could now be tested in cancer patients whose cancer has stopped responding to ICI (that is in cancer that is beginning to grow again in patients treated with ICI).

You can read the paper ‘PARP14 inhibition restores PD-1 immune checkpoint inhibitor response following IFNγ-driven acquired resistance in preclinical cancer models’ in full here