Table 1.

Characteristics of NK cell receptors relevant in CAR-independent anti-tumor activity, mentioned in the article.

Receptor	Impact on NK Cell	Ligands	Function
CD16	Activating	Fc domain of IgG	ADCC initiation through the classical ITAM pathway. Its activation is sufficient to ignite cytotoxicity and cytokine production in resting NK cells, regardless of the adaptor particle.
DNAM-1	Activating	CD112, CD155	Expressed on NK cells, T cells and monocytes. Its signaling promotes cellular adhesion.
KIR	Activating/Inhibitory	HLA class I	Its impact on NK cells depends on the isoform. Inhibitory isoforms outweigh activating ones in the affinity to HLA class I ligands.
NKG2A	Inhibitory	HLA-E	Forms complexes with CD94 and through the ITIM motif transduces inhibitory signals. Has a higher affinity to HLA-E ligands than the CD94/NKG2C complex.
NKG2C	Activating	HLA-E	Forms complexes with CD94 and associates with DAP12 for an activating signal transduction. Has a lower affinity to HLA-E ligands than the CD94/NKG2A complex.
NKG2D	Activating	MICA, MICB ULBP-1-6	Expressed on the surface of NK, γδ T and CD8+ T cells. Associates with the DAP10 homodimer. Binds ligands upregulated by infected, stressed or transformed cells.
NKp30	Activating	HA/HS/GAGs	Member of the NCR family. Expressed constitutively on mature, resting or activated NK cells and some populations of T cells. Downregulated on memory-like NK cells.
NKp44	Activating	HA/HS/GAGs	Found only on activated NK cells. Associates with the DA12 homodimer for cytokine release ignition.
NKp46	Activating	HA/HS/GAGs	Uniquely expressed on NK cells. Member of the NCR family. Triggers cytotoxic reaction.
PD-1	Inhibitory	PDL-1, PDL-2	Expressed on various immune cells. Binds to ligands present across multiple cancer types leading to NK cell exhaustion and cancer immune escape. The most abundantly expressed by mature NK cells.
TIGIT	Inhibitory	CD112, CD113, CD155	Expressed in NK and T cells. Among others, binds to the CD155 ligand rarely expressed on healthy cells, but found abundantly in cancer cell lines and human neoplasms. TIGIT blockade prevents NK and T cell exhaustion and tumor cell escape.
2B4	Activating	CD48	Expressed on diverse immune cells beyond NK cells. Binds to CD48, widely expressed on cells of hematopoietic origin. In immature NK cells, can act as an inhibitor.