Figure 1. Strategies to activate antitumor NK cells. NK activation occurs downstream of killer cell lectin-like receptor subfamily K member 1 (KLRK1; CD314; NKG2D). In Nature, scientists showed that a casitas B cell lymphoma-b (CBL-B)-TAM receptor (TAMR) pathway suppresses the activation of NK cells.1

[a] TAMR kinases, including TYRO3 protein tyrosine kinase (TYRO3; SKY), AXL receptor tyrosine kinase (AXL; UFO) and c-Mer proto-oncogene tyrosine kinase (MERTK), are activated by an extracellular ligand, such as growth arrest-specific 6 (GAS6).

[b] Binding by GAS6 leads to the recruitment of CBL-B to TAMR and receptor ubiquitination (orange circles). Activation of this pathway inhibits NK cell antitumor activity.

A number of companies are developing therapeutics that activate antitumor immunity by interfering with this pathway.