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Interleukin-15 potentiates human natural killer cells to resist tumor-induced suppression through mTOR-regulated metabolic control
  1. Andreas Lundqvist1,
  2. Yumeng Mao1,
  3. Xiaonan Zhang1,
  4. Erik Wennerberg1,
  5. Vincent Van Hoef1,
  6. Ola Larsson1,
  7. Stig Linder1 and
  8. Rolf Kiessling1
  1. Aff1 grid.4714.60000000419370626Karolinska Institutet Stockholm Sweden

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Meeting abstracts

In cancer patients, anti-tumor functions of NK cells are severely impaired by a variety of immunosuppressive mechanisms. Interleukin (IL)-2 and -15 are two essential cytokines regulating the development and function of human natural killer (NK) cells. Here, we compared the role of IL-2 and IL-15 to render resistance of human NK cells to tumor-induced suppression. We found that early-passage melanoma tumor cells strongly inhibited functions of IL-2 activated NK cells through production of prostaglandin E2 (PGE2). Under the same condition, IL-15 activated NK cells could significantly retain the ability to proliferate in vitro durability, in comparison to IL-2-expanded cells. Altogether, our study uncovers distinct properties between IL-2 and IL-15 on primary human NK cells under tumor-induced suppression. It provides evidence that implementation of IL-15 may greatly improve the clinical efficacy of adoptive NK cell therapy for the treatment of human cancers.