Intersections between innate immune response and gastric cancer development

Table 1 Expression of Toll-like receptors in esophageal and gastric epitheliums

PRR	Organ	Model	Method	Ligand	Observation	Reference
TLR1/2	Esophagus	Esophageal carcinoma and premalignant lesions	IHQ	Triacyl lipopeptide	Receptor upregulation in tumor and dysplasia	[22,171]
TLR2	Stomach; esophagus	Human ADC and premalignant lesions; H. pylori infection mice model andin vitro culture	IHQ; RT-qPCR	Microbial lipopeptide	Receptor upregulation in tumor cores. Increased tumorigenesis; constitutive expression in TE-1 cell line	[21,22,27,32,172-174]
TLR3	Stomach; esophagus	Human gastric and esophageal carcinoma	IHQ; RT-qPCR	dsRNA	Increased receptor levels correlate with poor prognosis; increased expression on EAC-derived cell lines	[25,174-176]
TLR4	Stomach; esophagus	Human ADC and premalignant lesions; H. pylori infection; esophageal carcinoma	IHQ; RT-qPCR	LPS	Upregulation in tumor cores; weak association with clinicopathologic variables; high expression correlates with poor prognosis; upregulation of IL-8 and COX-2 in BE	[21,24,25,27,32,171,173-179,182]
TLR5	Stomach; esophagus	Human ADC and premalignant lesions; H pylori infection	IHQ	Flagellin	Highly expressed; upregulation in tumor and older patients; association with necrosis and tumor growth in the stomach; overexpression in dysplastic lesions of BE; no association with EAC prognosis	[26,27,32,177]
TLR6	Esophagus	Esophageal carcinoma and human dysplasia	IHQ; IF	Diacyl lipopeptide	Upregulated in tumor tissue	[22,171]
TLR7	Stomach; esophagus	Human ADC and normal tissue	IHQ; WB; RT-qPCR	ssRNA	Downregulated in gastric tumors; high levels correlate with a better outcome in GC; constitutive expression in TE-1 cell line; association between expression and tumor grade in ESCC	[22,32,173,174,176,180,183]
TLR9	Stomach; esophagus	Human ADC	IHQ; RT-qPCR	ssDNA; dsDNA	Upregulated in early tumors; correlation with better prognosis in GC; association with histopathological grade in ESCC and dysplasia; high expression in EAC correlates with advanced tumor stage and metastasis	[24,25,32-34,173,175,176,181,184]
TLR10	Stomach	Human biopsy	RT-qPCR	ssDNA; dsDNA	Upregulated by H. pylori	[35]

ADC: Adenocarcinoma; BE: Barrett’s esophagus; EAC: Esophageal adenocarcinoma; ESCC: Esophageal squamous cell carcinoma; GC: Gastric cancer; H. pylori: Helicobacter pylori; IF: Immunofluorescence; IHQ: Immunohistochemistry; PRR: Pattern recognition receptor; RT-qPCR: Reverse transcription and quantitative PCR; TE-1: Human cell line derived from esophageal cancer; TLR: Toll-like receptors; WB: Western blot.