Fig. 2
From: Reigniting hope in cancer treatment: the promise and pitfalls of IL-2 and IL-2R targeting strategies
The schematic diagram illustrates the multifaceted role of Interleukin-2 (IL-2) in the homeostasis and functional dynamics of Natural Killer (NK) cells, which are characterized as CD56+CD3− large granular lymphocytes integral to the human innate immune response. IL-2 is instrumental in the differentiation process, facilitating the transformation of NK precursors into mature NK cells. It also maintains the homeostasis of mature NK cells by regulating their survival, proliferation, and apoptosis. The diagram further highlights the influence of IL-2 on the functional aspects of mature NK cells. It enhances the cytolytic activity of both CD56bright and CD56dim NK cells and significantly amplifies cytokine secretion, particularly within the CD56bright human NK subset. In secondary lymphoid tissues such as lymph nodes, IL-2 promotes the acquisition of Killer Cell Immunoglobulin-like Receptors (KIR; also known as CD158) and CD16 expression by CD56bright NK cells. The diagram also showcases the characteristics of cytokine-induced memory-like (CIML) NK cells, which include increased expression of CD25 (IL-2Ra), decreased expression of KIRs, and Transforming Growth Factor-beta (TGFβ) receptors. These changes potentially alleviate inhibitory mechanisms in CIML NK cells. The enhanced production of Interferon-gamma (IFNγ) may augment anti-tumor responses. The schematic also highlights the metabolic changes in CIML NK cells. Metabolic alterations, including the roles of glucose transporter and transferrin receptor, are emphasized for their critical contribution to the long-term persistence and recall functions of CIML NK cells. Abbreviations: fms-like tyrosine kinase 3 ligand (FL), kit ligand (KL).The figure was created using the online tool https://biorender.com/