MAIT cells numbers and frequencies in patients with acute myeloid leukemia at diagnosis: association with cytogenetic profile and gene mutations.

ABSTRACT

Harnessing or monitoring immune cells is actually a major topic in pre-clinical and clinical studies in acute myeloid leukemia (AML). Mucosal-Associated Invariant T cells (MAIT) constitute one of the largest subset of innate-like, cytotoxic T cell subsets in humans. Despite some papers suggesting a role for MAIT cells in cancer, their specific involvement remains unclear, especially in myeloid malignancies. This prospective monocentric study included 216 patients with a newly diagnosed AML. Circulating MAIT cells were quantified by flow cytometry at diagnosis and during intensive chemotherapy. We observed that circulating MAIT cells show a specific decline in AML patients at diagnosis compared to healthy donors. Post-induction monitored patients presented with a drastic drop in MAIT cell numbers, with recovery after one month. We also found correlation between decrease in MAIT cells number and adverse cytogenetic profile. FLT3-ITD and IDH ½ mutations were associated with higher MAIT cell numbers. Patients with high level of activated MAIT cells are under-represented within patients with a favorable cytogenetic profile, and over-represented among patients with IDH1 mutations or bi-allelic CEBPA mutations. We show for the first time that circulating MAIT cells are affected in newly diagnosed AML patients, suggesting a link between MAIT cells and AML progression. Our work fosters new studies to deepen our knowledge about the role of MAIT cells in cancer.