Oral Presentation Melbourne Immunotherapy Network Winter Retreat 2018

Chronic inflammation and bowel cancer; are your MAITs involved? (#32)

Jason Kelly 1 2 , Goerge Kannourakis 1 , Daniel Gray 3 , Dale I Godfrey 4 , James McCluskey 4 , Stuart P Berzins 1 2
  1. Fiona Elsey Cancer Research Institute, Ballarat, VIC, Australia
  2. Federation University Australia, Ballarat, VIC, Australia
  3. The Walter and Eliza Hall Institute of Medical Research , Melbourne, VIC, Australia
  4. Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, University of Melbourne, Melbourne, VIC, Australia

Mucosal associated invariant T cells (MAIT cells) are a recently described innate-like T cell subset which comprise up to 5% of the circulating T cells within humans.  These MR1 restricted T cells recognise non-peptide, small molecule antigens derived from microbial vitamin B synthesis. They are also enriched within the mucosal tissues in the body such as the gastro-intestinal tract.  Upon activation, MAIT cells can rapidly produce cytokines and are believed to play a role in regulating the local immune milieu. 

Cancers of the large bowel have the second highest mortally rates within Australia and these cancers respond poorly to conventional immune based therapy. Bowel cancers arise in a background of chronic inflammation, and the regulation of the immune milieu at the site of these mucosal tumours is currently poorly understood. 

Whilst investigating the chronically stimulated MAIT cells potentially seen in bowel cancer we have identified a cytokine response rich in interleukin 13 (IL-13).  This IL-13 MAIT cell response has not been previously described and has the potential to skew the local immune milieu away from anti-tumour inflammation and promote tumour growth and spread. This IL-13 response not only has the potential to impact cancer research, but also alter the research of a number of human inflammatory disorders.