<em>Are you my MAIT?</em> Understanding the role of MAIT cells in colorectal liver metastasis — ASN Events
  1. Schedule
  2. Poster Session Two
  3. Are you my MAIT? Understanding the role of MAIT cells in colorectal liver metastasis

Are you my MAIT? Understanding the role of MAIT cells in colorectal liver metastasis (#321)

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

Background: Stage-IV Colorectal Cancer (CRC) involves metastasis to the liver. Cytotoxic CD8+ T-cells play a critical role in cancer; serving as a key marker for the Galon-ImmunoscoreR.

Mucosal-Associated Invariant T-cells (MAITs) are a recently described subset of T-cells that also express CD8, and are important in controlling bacterial infections. MAITs are highly abundant in the liver comprising up to 40% of T-cells. The role of MAITs in solid tumours is yet to be elucidated but they are nonetheless being included with CD8+ cells when defining Tumour Infiltrating Lymphocytes (TILs). MAIT cells may serve as biomarkers for disease progression and outcome, or provide a novel immune-therapeutic target.

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

Results: We have recruited 22 patients with liver mets and documented MAITs in the tumour; surrounding liver tissue and PBMCs. MAIT cell frequency is decreased in the tumour compared to the surrounding tissue. MAITs have a high expression CD69 in the tumour compared to liver, indicating activation. MAIT cells have a high expression of both PD-1 and CD45RO across tissue types indicating potential response to immune checkpoint blockade and memory status, respectively. We have preliminary data demonstrating that autologous MAIT cells have effector function when co-cultured with patient-derived tumouroids in vitro.

Conclusions: MAITs are decreased in the tumour, with high PD-1 expression, which could be an ideal target for immunotherapies. These intriguing results warrant further investigation to determine their direct or indirect role of MAIT cells in tumour immunity.

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