Cookies on this website

We use cookies to ensure that we give you the best experience on our website. If you click 'Accept all cookies' we'll assume that you are happy to receive all cookies and you won't see this message again. If you click 'Reject all non-essential cookies' only necessary cookies providing core functionality such as security, network management, and accessibility will be enabled. Click 'Find out more' for information on how to change your cookie settings.

Professor Yang Shi’s laboratory uncovers an important role for the chromatin regulator LSD1 in T cell exhaustion and demonstrates that LSD1 inhibition in mice increases the durability of responses to immune checkpoint blockade therapy.

Immune checkpoint blockade therapy is a type of cancer treatment that has achieved great success in some patients. It works by blocking an inhibitory immune signal and reinvigorating exhausted T cells to kill the cancer cells. However, only a minority of patients benefit from this treatment and responses can be short-lived. Understanding more about the molecular mechanisms responsible for T cell exhaustion and the ability of T cells to be reinvigorated may enable the design of new strategies to enhance the durability of immune checkpoint blockade therapy to benefit more patients.

Alterations to chromatin – the structure formed by DNA and histone proteins – have the potential to stably silence genes and prevent exhausted T cells from being reinvigorated. Ludwig Oxford’s Professor Yang Shi’s laboratory studied the changes in chromatin during T cell exhaustion. They uncovered that LSD1, an enzyme that removes methyl groups from histone proteins, is an important regulator of T cell exhaustion in cancer.

Their research, published in Nature Communications, shows that inhibiting LSD1 in mice increases the subset of exhausted T cells that are able to be reinvigorated by immune checkpoint blockade treatment. This led to an increase in activated T cells with cancer-killing function and a longer-lasting response to treatment.

This study provides important new insights into the epigenetic mechanisms regulating T cell exhaustion and suggests that the combination of LSD1 inhibition with immune checkpoint blockade therapy should be investigated further to enhance cancer treatment.

 

Image credit: NIAID, CC BY 2.0 via Wikimedia Commons

Similar stories

Ludwig Oxford and IDRM host 6th form students for a taster week of research

Staff and students at Ludwig Oxford and the Institute of Developmental and Regenerative Medicine put on lectures, panel sessions, lab workshops and more for 6th form students with a keen interest in scientific research.