CHILDREN’S CANCER RESEARCH INSTITUTE (CCRI)
”Unconventional T cells: two rings to rule them all”
Most, if not all, human diseases are associated with conserved and specific metabolic changes. Infections, malignant transformation, and perturbations in the microbiome induce dynamic reprogramming of metabolism in various cells types and tissues. While such reprogramming aims to maintain homeostasis and support functions of affected cells, it is also a subject for immune surveillance by unconventional (metabolite-specific) T cells. Recent studies showed that unconventional T cells recognize different types of organic structures, including lipids, phospho-antigens, small metabolites and even drugs and drug metabolites. While these T cells are involved in the pathogenesis of various autoimmune, inflammatory, and infectious diseases, their role and activity in the context of disease-associated metabolic perturbations are not completely understood.
In my talk I will first make a brief overview on the biology of unconventional T cells, their role in different diseases, and antigen specificity. I will address the fundamental questions of metabolism-associated immune surveillance in health and disease, shedding light on “immunogenicity” of several metabolic pathway. I will then present an innovative approach that combines metabolic drug screening, pathway analysis, and metabolomics to identify small metabolite antigens recognized by unconventional T cells. I will also explain how within the scoop of this project I am hunting for the specific T cells. As a proof-of-concept, I will show how we employ this approach to investigate the intrinsic (genetic background, tissue origin) and extrinsic (microenvironment, radio-/chemotherapy) factors shaping cellular metabolism and immunogenicity in pediatric tumors. I will then elaborate how this knowledge can be employed for the improvement of the current and developing novel treatment strategies. Finally, I will outline how my approach can be adopted to study other human diseases.
Host: Johannes SCHMID
Contact for questions: Helmut KUBISTA