Cytokine receptors on natural killer (NK) cells during ex vivo pre-activation

Cytokine receptors on natural killer (NK) cells during ex vivo pre-activation refer to the ensemble of receptors—specifically the interleukin-12 (IL-12), interleukin-15 (IL-15), and interleukin-18 (IL-18) receptors—that are stimulated to generate cytokine-induced memory-like (CIML) NK cells (Frontiers in Immunology, 2018). This pre-activation process involves a brief exposure (typically 12-16 hours) to a cocktail of these cytokines, which induces a stable memory-like phenotype characterized by enhanced effector functions, such as increased interferon-gamma (IFN-γ) production and superior cytotoxicity against tumor cells (Journal of Experimental Medicine, 2012). A critical molecular hallmark of this state is the significant up-regulation of the high-affinity interleukin-2 receptor alpha chain (CD25), which allows the cells to respond to picomolar concentrations of IL-2 for improved survival and expansion in vivo (Biology of Blood and Marrow Transplantation, 2014). These receptors mediate signaling through the JAK-STAT pathway, leading to epigenetic modifications that sustain the enhanced functional state (Frontiers in Immunology, 2018). Clinically, this approach is utilized in adoptive immunotherapy to treat hematologic malignancies like acute myeloid leukemia (AML) and is being explored for solid tumors (IntechOpen, 2017). Drugs interacting with these receptors include recombinant cytokines like rhIL-12, rhIL-15, and rhIL-18, as well as IL-15 superagonists like Nogapendekin alfa inbakicept (ResearchGate, 2017).

Other names

CIML NK cell cytokine receptorsIL-12/15/18 receptorsMemory-like NK cell receptorsPre-activated NK cell cytokine receptors

Agonism of IL-12, IL-15, and IL-18 receptors to induce a memory-like phenotype and up-regulation of the high-affinity IL-2 receptor (CD25) for enhanced effector function.