Hematological Malignancies Escape from NK Cell Innate Immune Surveillance: Mechanisms and Therapeutic Implications

Table 2

Novel agents used in hematological malignancies and their impact on NK-cell activation.

Class of drugs	Therapeutic molecules	Main indications	Inhibitory receptor ligands	Activating receptors	Activating receptor ligands	References
IMIDs	Thalidomide	Multiple myeloma		NKp46		[67]
	Lenalidomide			upregulation
HDACI	Vorinostat	Lymphoma		NKp30 and NKp46	NKG2D and	[68, 69]
	Panobinostat				DNAM ligand
				downregulation	upregulation
Demethylating agents	5-azacytidine	MDS	Up regulation		NKG2D ligand	[70, 71]
	5-aza-2^′-deoxycytidine		KIR		upregulation
Proteasome inhibitors	Bortezomib	Multiple myeloma	Downregulation; HLA molecules		NKG2D; TRAIL and DNAM	[72–75]
					ligand upregulation
All-trans retinoic acid	Vesanoid	AML3		NKG2D		[76]
				Upregulation
Tyrosine kinase inhibitors	Imatinib mesylate	CML		NKG2D	sMICA	[77]
				upregulation	downregulation

Abbreviations: IMIDs: immunomodulaory drugs; HDACI: Histone deacetylase inhibitors; MDS: myelodysplastic syndrome; AML: acute myeloid leukemia; CML: chronic myeloid leukemia; NK: natural killer cell; sMICA: stress-induced molecule HLA class-I chain-related A.