Work in the Division of Immunology covers three mains areas:

 The Fearon lab has shifted its interest from the memory CD8+ T cell to tumor immunology.  The immune system should be able to control the growth of many tumors because cancer cells with genomic instability generate neoantigens, which serve to make them appear as “foreign” to the immune system.  However, this obviously does not occur.  One problem appears to be that the tumor microenvironment is immune suppressive, so that the systemic T cell responses to tumor antigens that can be demonstrated are prevented from attacking the cancer cells.  Our lab has recently shown that one type of tumor stromal cell (i.e., a cell in tumors other than the cancer cell), the FAP+ cell, mediates local immune suppression, and its elimination allows immune control of tumor growth.  We have also found that the FAP+ cell resides in normal tissues where it has unexpected functions, such as the prevention of cachexia, the muscle wasting syndrome often associated with cancer.  We wonder whether the biological role of the FAP+ cell is related to tissue maintenance and repair, accounting for its regrettable presence in tumors?  We are trying to discover how to interrupt the immune suppressive function of the FAP+ stromal cell./I

 The Griffths lab studies cytotoxic T lymphocytes (CTL) and Natural Killer (NK) cells, which use polarized secretion to destroy virally infected and tumorigenic target cells.  Specialised secretory lysosomes, containing the pore forming protein perforin and a series of serine proteases, termed granzymes deliver the lethal hit in a specialized domain of the immunological synapse.  The research is focused on understanding the molecular basis of polarized secretion from CTLs and has used a series of rare genetic diseases including Hermansky-Pudlak and Haemophagocytic syndromes to identify the roles of proteins involved in secretion from CTL and NK cells.

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