1. Cutting Edge: mTORC1 Inhibition in Metastatic Breast Cancer Patients Negatively Affects Peripheral NK Cell Maturation and Number
- Author
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Olivier Tredan, Romaine Mayet, Magali Morelle, Benoit You, François Parant, Marine Villard, Isabelle Ray-Coquard, Thomas Bachelot, Sébastien Viel, David Pérol, Emily Charrier, Yamila Rocca, Gwenaële Garin, Antoine Marçais, Laurie Besson, Pierre Heudel, Thierry Walzer, Benoîte Méry, Health System Analysis Laboratory (GATE), and Université de Lyon
- Subjects
Adult ,Immunology ,Population ,Cell ,[SDV.CAN]Life Sciences [q-bio]/Cancer ,Antineoplastic Agents ,Breast Neoplasms ,mTORC1 ,Mechanistic Target of Rapamycin Complex 1 ,Biology ,mTORC2 ,03 medical and health sciences ,0302 clinical medicine ,Immunophenotyping ,medicine ,Humans ,Immunology and Allergy ,Cytotoxic T cell ,Everolimus ,Prospective Studies ,Neoplasm Metastasis ,education ,Mechanistic target of rapamycin ,ComputingMilieux_MISCELLANEOUS ,PI3K/AKT/mTOR pathway ,Aged ,Cell Proliferation ,Aged, 80 and over ,education.field_of_study ,TOR Serine-Threonine Kinases ,Cell Differentiation ,Middle Aged ,3. Good health ,Killer Cells, Natural ,Treatment Outcome ,medicine.anatomical_structure ,Cancer research ,biology.protein ,Female ,France ,Follow-Up Studies ,Signal Transduction ,030215 immunology - Abstract
NK cells are cytotoxic lymphocytes displaying strong antimetastatic activity. Mouse models and in vitro studies suggest a prominent role of the mechanistic target of rapamycin (mTOR) kinase in the control of NK cell homeostasis and antitumor functions. However, mTOR inhibitors are used as chemotherapies in several cancer settings. The impact of such treatments on patients’ NK cells is unknown. We thus performed immunophenotyping of circulating NK cells from metastatic breast cancer patients treated with the mTOR inhibitor everolimus over a three-month period. Everolimus treatment resulted in inhibition of mTORC1 activity in peripheral NK cells, whereas mTORC2 activity was preserved. NK cell homeostasis was profoundly altered with a contraction of the NK cell pool and an overall decrease in their maturation. Phenotype and function of the remaining NK cell population was less affected. This is, to our knowledge, the first in vivo characterization of the role of mTOR in human NK cells.
- Published
- 2021
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