Figure 2.

Schematic representation of natural killer (NK) cells’ recognition strategies of target cells. (A) NK cells’ activity is regulated by a variety of signaling molecules that engage the activating and inhibitory receptors on the surface of NK cells. Healthy cells express the major histocompatibility complex class I (MHC-I), which suppresses NK cells activation, as well as low levels of activating ligands. (B) Tumor cells downregulate MHC-I in order to escape cytotoxic T cells. However, this prompts NK cells to recognize and kill such tumor cells through their “missing-self” program. (C) Tumor cells upregulate stress ligands, which are recognized by activating receptors on NK cells, countermanding any inhibitory signals and inducing NK cell-mediated cytotoxicity. (D) Antibody-dependent cell-mediated cytotoxicity (ADCC) is triggered by CD16 (one of the most potent activating receptors on NK cells), which recognizes the antibodies bound to antigen-coated tumor cells.