The global incidence of cancer is on the increase and researchers are prospecting for specific
and non-selective therapies derived from the immune system. The killer activating receptors
of NK cells are known to be involved in immunosurveillance against tumor and virally-infected
cells. These receptors belong to two main categories, namely the immunoglobulin like and C-lectin
like families. Though they have different signal pathways, all the killer activating receptors have
similar effector functions which include direct cytotoxicity and the release of inflammatory cytokines
such as IFN-gamma and TNF-alpha. To transduce signals that exceed the activation threshold
for cytotoxicity, most of these receptors require synergistic effort.
This review profiles 21 receptors: 13 immunoglobulin-like, 5 lectin-like, and 3 others. It critically
explores their structural uniqueness, role in disease, respective transduction signal pathways and
their status as current and prospective targets for cancer immunotherapy.
While the native ligands of most of these receptors are known, much work is required to prospect
for specific antibodies, peptides and multi-target small molecules with high binding affinities.