Table 2.

Mechanisms of resistance to NK cell-mediated cytotoxicity.

Protein	Mechanism of Resistance	Cancer	Reference
Caspase-3	Gene mutations that interfere with caspase activity	Gastric carcinoma	[63]
		Vulvar squamous carcinoma	[64]
		Hepatocellular carcinoma	[65]
Caspase-4		Advanced gastric adenocarcinoma and colorectal cancer	[66]
Caspase-5		MM, NHL, NSCLC, hepatocellular, colorectal and gastric carcinomas	[67]
Caspase-6		GIST	[68]
Caspase-7		NSCLC, colorectal and gastric carcinomas	[69]
Caspase-8		Colorectal, esophageal and head and neck carcinomas	[70]
Caspase-9		Colorectal and gastric carcinomas	[71]
Survivin	Aberrant expression by chromosomal amplification	Neuroblastoma	[72]
c-IAP1		Esophageal, liver, lung and ovarian carcinomas	[73,74]
c-IAP2	Aberrant activity by chromosomal translocation	MALT lymphomas	[75]
Bax	Inactivating gene mutations	Colon and gastric carcinomas with microsatellite instability	[76,77,78]
		T-ALL	[79]
		CLL	[80]
		Burkitt’s lymphoma	[81]
BCL2	Aberrant expression by chromosomal translocation	DLBCL	[82]
	Homologue protein expression by cancer-associated viruses	Kaposi’s sarcoma	[83]
c-FLIP	Homologue protein expression by cancer-associated viruses	Kaposi’s sarcoma	[84]
	Aberrant protein expression	Burkitt’s lymphoma	[85]
		AML	[86]
		Colorectal cancer	[87]
Bim	Gene deletion	MCL	[88,89]
Noxa	Silencing gene mutations	DLBCL	[89]
TRAIL-R1	Gene mutations that interfere with receptor activity	Lung, head and neck and gastric carcinomas	[90]
		NHL	[91]
	Allelic deletion	B-NHL	[92]
		Breast cancer	[93]
TRAIL-R2	Allelic deletion	B-NHL	[92]
		Breast cancer	[93]
	Loss-of-function mutations	Head and neck and lung carcinomas	[94]
		NSCLC	[95]
		Gastric cancer	[96]
	Gene mutations that interfere with receptor activity	NHL	[91]
Fas	Loss-of-function mutations	Hematological malignancies	[97]
Osteoprotegerin	Aberrant protein expression	MM	[98]
DcR3		Glioblastoma	[99]
		Breast cancer	[100]
		Gastric cancer	[101]
		Colorectal cancer	[102]
TRAIL-R3		AML	[103]
		Breast cancer	[104]
TRAIL-R4		Prostate cancer	[105]
PRF1	Downregulation of protein expression	Pancreatic, gastric and colorectal carcinomas	[106]
		Lung cancer	[107]
		Hepatocellular carcinoma	[108]
	Reduction of protein levels by tumor-associated cells	T-cell lymphoma	[109]
		Hepatocellular carcinoma	[110]
		Melanoma	[111]
		Colorectal cancer	[112]
	Impaired cell surface binding	AML	[113]
	Impaired protein mobilization to the immune synapse	Burkitt’s lymphoma	[114]
GMZB	Downregulation of protein expression	Lung cancer	[115]
		Hepatocellular carcinoma	[108]
		Lung cancer	[107]
	Increased protein degradation	Breast cancer	[116,117]
Serpin B9	Aberrant protein expression	DLBCL	[118]
		NSCLC	[119]
		Lung cancer	[120]
Serpin B4		Squamous cell carcinomas	[121,122,123]
CD107a	Downregulation of protein expression	Pancreatic cancer	[124]
F-actin	Intracellular accumulation	Breast cancer	[125]
Connexin-43	Increased protein degradation	Melanoma	[126]

NSCLC = non-small cell lung cancer, GIST = gastrointestinal stromal tumor, MALT = mucosa-associated lymphoid tissue, CLL = chronic lymphocytic leukemia, ALL = acute lymphoid leukemia, DLBCL = diffuse large B-cell lymphoma, AML = acute myeloid leukemia, MCL = mantle cell lymphoma, MM = Multiple myeloma, NHL = non-Hodgkin lymphoma.