Poster Presentation 29th Lorne Cancer Conference 2017

Mucosal Associated Invariant T-Cells (MAIT) - Companions or conspirators within the tumour microenvironment? (#230)

Rosemary Millen 1 , Joseph Kong 1 , Glen Guerra 1 , Sara Roth 1 , Nick A Gherardin 2 , Benjamin Thomson 1 , Brett Knowles 1 , Simon Banting 3 , Paul Neeson 1 , Alexander Heriot 1 , Kumar Visvanathan 3 , Rob Ramsay 1
  1. Peter MacCallum Cancer Centre, Victorian Comprehensive Cancer Centre, Melbourne, VIC, 3000, VIC, Australia
  2. The Peter Doherty Institute, Melbourne, Victoria, Australia
  3. St. Vincent's Hospital, Melbourne, Victoria, Australia

 Subheadings: What is the role of Mucosal Associated Invariant T-cells (MAITs) in metastatic Colorectal Cancer?

Aim: Investigate MAITs in colorectal liver metastasis.

Background: Colorectal Cancer (CRC) is the second most common cancer in Australia. Stage-IV CRC involves metastasis to other organs, most commonly the liver. The immune system, particularly cytotoxic CD8+ T-cells play a critical role in the progression of cancer; serving as a key marker for the Galon-ImmunoscoreR(1). We have shown that CD8+ T cells are predictive of outcome even in early stage primary CRC(2). MAIT cells are a recently described subset of T-cells that also express CD8, however they are phenotypically and functionally distinct from conventional CD8+ T cells and play a role in bacterial infections. MAITs represent 40% of T cells within the normal liver. The role of MAITs in cancer is yet to be elucidated but they may be pooled with traditional CD8+ cells when defining tumour infiltrating T-cells. It's important to establish their contribution to tumour infiltration, as they may serve as biomarkers for disease progression or provide a novel immune-therapautic target.

Methods: We plan to recruit 40 patients with colorectal-liver metastasis and investigate the role of MAIT cells in the tumour, surrounding tissue and peripheral blood by flow cytometry, cytokine production and functional tumour cell killing assays developed in our lab.

Results: To date we have recruited 15 patients with liver mets and documented MAITs in the tumour, surrounding liver tissue and PBMCs. MAITs are present within the centre of the tumour, with an increased percentage at the invasive margin. Liver mets are often capsulated, so these data suggest active recruitment of MAITs into the tumour from the surrounding liver. As many of these MAIT cells express CD8, the interpretation of an ImmunoscoreR needs deeper consideration compared to that described for primary CRC.

Conclusions: MAITs are present within colorectal-liver tumours, with a high abundance in the surrounding liver tissue. We are currently investigating their phenotype including activation status, cytokine profile and cytotoxic potential. These intriguing results warrant further investigation to determine their direct or indirect role of MAIT cells in tumour immunity.