Intervention on toll-like receptors in pancreatic cancer

Table 3 Toll-like receptors and their intervention in pancreatic ductal adenocarcinoma

	Substance/compound	Intervention	Effects	Ref.
TLR2	MALP-2 (G)	Activation	Induce lymphocyte invasion and tumor necrosis	[33]
			Inhibit tumor growth	[33]
			Prolongs mean survival	[35]
			Reverse tumor-associated immunosuppression	[33]
	Polysaccharide-K (G)	Activation	Inhibit tumor growth and induce apoptosis in tumor cells	[40]
	Dmt-Tic-Cy5	Activation	Acts as vaccine adjuvant in pancreatic cancer	[41]
			Target imaging and therapy	[41,42]
	PAUF	Mixed	Facilitates tumor growth	[43]
			Promotes tumor immune-resistance	[43]
TLR3	Polycytidylic acid	Activation	Accelerates carcinogenesis	[49]
			Induces T cell invasion and tumor lysis	[48]
	Phenylmethimazole	Inhibition	Inhibits tumor growth and migration	[50]
TLR4	Lipopolysaccharide	Activation	Accelerates carcinogenesis	[49]
			Induce desmoplastic stroma	[49]
			Induce increased H2O2 extracellular production	[57]
			Increased invasiveness	[58,61]
			Induce M2-polarization in tumor-associated macrophages	[61]
TLR7	Imiquimod	Activation	Induce T cell invasion and tumor lysis	[48]
	IRS661	Inhibition	Prevent tumor progression and stromal expansion	[67]
			Regulates cell cycle in cancer cells	[67]
TLR9	CpG-ODN 1816/26 (G’)	Activation	Delays tumor development, reduce invasiveness	[72]
			Prolongs mean survival	[72]
	IMO (C)	Activation	Prolongs mean survival, inhibit tumor growth and migration	[77]
			Reestablish cetuximab sensibility in cancer cells	[77]
	CpG-ODN 2216	Activation	Inhibits tumor growth and migration	[79]

TLR: Toll-like receptor; MALP-2: Macrophage activating lipopeptide-2; PAUF: Pancreatic adenocarcinoma upregulated factor; IRS661: Immunoregulatory sequence 661; CpG-ODN: CpG oligodeoxynucleotide; IMO: Immunomodulatory nucleotides. (G): Synergism when combined with gemcitabine; (G’): Effect mainly when combined with gemcitabine; (C): Effect merely when combined with cetuximab.