Adrian Hayday : Areas of interest

Standard content

The group is focused on understanding how lymphocytes function within epithelial tissues.

We have developed the 'lymphoid stress surveillance' hypothesis whereby tissue-associated T cells recognise and respond rapidly to perturbations to epithelia cells. This under-studied biology is distinguishable from conventional T cell responsiveness by its rapidity and by its capacity to monitor perturbations induced by non-microbial challenges, such as carcinogens or oxidative stress.

The implications are that tissue-associated T cells can identify and eradicate transformed cells early en route to malignancy.

Consistent with this, lymphoid stress-surveillance includes the engagement by T cells of specific molecules upregulated on epithelial cell surfaces as a result of epidermal growth factor receptor dysregulation, as often occurs in tumours. Indeed, the lack of tissue-associated T cells significantly increases susceptibility to chemical carcinogens. Moreover, tumours and many types of virus employ immuno-evasive strategies to disarm this pathway of surveillance. Ongoing efforts aim to define the full range of molecules and pathways by which epithelial cell dysregulation is communicated to T cells, and the functional consequences thereof.

In this regard, our most recent studies have identified a new family of genes, expressed primarily by epithelial cells, upon which the composition of tissue-associated T cell compartments depends. We are also investigating the immunotherapeutic potential of tissue-associated T cell transfusion to patients, research which is conducted by members of our laboratory based at the Guy's Hospital Campus of King's College London.