Left: Spinal cord green flurescent microglial cells in multiple sclerosis.Tumours of the central nervous system (CNS) such as malignant gliomas actively suppress anti-tumour immune responses, thus escaping surveillance by the host immune system. Autoimmune diseases of the CNS, on the other hand, such as multiple sclerosis (MS), are characterized by a disproportionate immune response against self-antigens. Immune responses against tumours and self-antigens within the CNS share common cellular and molecular mechanisms. Understanding of these mechanisms is a prerequisite to develop effective immunotherapeutic strategies for cancer and autoimmune diseases.
Catabolism of the essential amino acid tryptophan (Trp) is a highly conserved mechanism that tightly regulates the function of T lymphocytes. Suppression of T cell immunity by Trp catabolism is implicated in transplant rejection, immune surveillance of tumours and autoimmunity. Thus, altering Trp catabolism is an attractive and novel therapeutic strategy for diseases such as cancer and autoimmune diseases.
We seek to gain insights into the regulation of T cell immunity as well as translating these insights to develop novel therapeutic strategies for MS and malignant glioma. Specifically, we are investigating how Trp catabolism modulates T cell function and how the rate-limiting enzyme in Trp catabolism – indoleamine-2,3-dioxygenase (IDO) – is regulated in immune surveillance of malignant gliomas and in MS.