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

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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.

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Acknowledgements

This work was funded in part by a research grant from the Ligue Nationale contre le Cancer- comité midi-pyrénées.

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  1. Francois Vergez and Emmanuel Treiner have contributed equally.

Authors and Affiliations

  1. Department of Internal Medicine, IUCT-Oncopole, CHU Toulouse, Toulouse, France

    Thibault Comont

  2. Laboratory of Hematology, IUCT-Oncopole, CHU Toulouse, Toulouse, France

    Thibault Comont, Marie-Laure Nicolau-Travers & Francois Vergez

  3. Cancer Research Center of Toulouse, Unité Mixte de Recherche (UMR) 1037 INSERM, ERL5294 Centre National de La Recherche Scientifique, Toulouse, France

    Thibault Comont, Sarah Bertoli, Christian Recher & Francois Vergez

  4. Department of Clinical Hematology, IUCT-Oncopole, CHU Toulouse, Toulouse, France

    Sarah Bertoli & Christian Recher

  5. Laboratory of Immunology, CHU Toulouse, Toulouse, France

    Emmanuel Treiner

  6. University Paul Sabatier III, Toulouse, France

    Sarah Bertoli, Christian Recher, Francois Vergez & Emmanuel Treiner

  7. Infinity, Inserm UMR1291, 330 Avenue de Grande Bretagne, 31000, Toulouse, France

    Emmanuel Treiner

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Correspondence to Emmanuel Treiner.

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Conflict of interest

T.C received honoraria and/or research or educational support from AbbVie, AstraZeneca, Bristol Myers Squibb (Celgene), Novartis and Takeda. S.B. has served on advisory boards for Daiichi-Sankyo, Astellas, Sanofi, and Jazz Pharmaceuticals. CR received research grants (my institution) by Abbvie, Amgen, Novartis, Celgene, Jazz Pharma, Agios, Daiichi-Sankyo, Astellas, Roche, MaatPharma; and has served on advisory boards for Abbvie, Janssen, Jazz Pharma, Daiichi-Sankyo, Astellas, Novartis, Celgene, Takeda, Roche, Otsuka, Macrogenics, Pfizer. F.V received research support from Pierre-Fabre. Other authors declare that they have no conflict of interest.

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Blood samples from healthy donors were obtained through a convention between the Etablissement Français du Sang (EFS)—Midi-Pyrénées and the University Hospital of Toulouse. Patients with AML gave their written consent to participate in the study.

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Precis Circulating MAIT cells at diagnosis of AML are significantly decreased, with signs of activation. MAIT cells numbers are affected by the cytogenetic profile and the mutational status of patients, suggestive of an association with disease progression.

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Comont, T., Nicolau-Travers, ML., Bertoli, S. et al. MAIT cells numbers and frequencies in patients with acute myeloid leukemia at diagnosis: association with cytogenetic profile and gene mutations. Cancer Immunol Immunother 71, 875–887 (2022). https://doi.org/10.1007/s00262-021-03037-9

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