title: Expression of Toll-like receptor9 in diffuse large B-cell lymphoma: further exploring CpG oligodeoxynucleotide in NFκB pathway.
abstract: Human Toll-like receptors (TLRs) that recognize a variety of pathogen-associated molecular patterns are associated with activation and immunogenic response in lymphoid neoplasms, but rarely explored in diffuse large B-cell lymphoma (DLBCL). We conducted this study to evaluate the expression of TLR9 in and potential treatment of DLBCL with TLR9 agonist - CpG oligodeoxynucleotide (ODN). The real-time quantitative reverse transcription-polymerase chain reaction was carried out to detect TLR9 expression in 41 formalin-fixed paraffin-embedded samples. The transformation of immunophenotype and NFκB pathway of DLBCL upon CpG ODN stimulation were investigated by a DLBCL cell line. TLR9 was commonly detected in DLBCL with relative mRNA levels above 1.0 × 10(-2)  in 35 of 41 cases (85.36%). It was suspected that a high proportion of DLBCL to be activated by CpG stimulation. In vitro study with a DLBCL cell line revealed an increased CD20, but decreased BCL-6 and MUM1/IRF4 expression after treatment with CpG ODN. The NFκB pathway was initially activated, but finally suppressed upon CpG ODN stimulation. The proliferation of tumor cells was also inhibited by long time incubation. These findings provide new insights into the role of TLR9 in DLBCL and potential implication of TLR9 agonist in the treatment of DLBCL.
authors.affiliation: Department of Pathology, Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan.
authors.forename: Wan-Ting
authors.initials: WT
authors.lastname: Huang
authors.forename: Shao-Wen
authors.initials: SW
authors.lastname: Weng
authors.forename: Chao-Cheng
authors.initials: CC
authors.lastname: Huang
authors.forename: Huei-Chiou
authors.initials: HC
authors.lastname: Lin
authors.forename: Po-Chin
authors.initials: PC
authors.lastname: Tsai
authors.forename: Jiin-Haur
authors.initials: JH
authors.lastname: Chuang
mesh_terms: D018951:Antigens, CD20 / Q000235:genetics / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects; D001402:B-Lymphocytes / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D016130:Immunophenotyping / Q000379:methods; D050835:Interferon Regulatory Factors / Q000235:genetics / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism*; D009838:Oligodeoxyribonucleotides / Q000494:pharmacology*; D051560:Proto-Oncogene Proteins c-bcl-6; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D051217:Toll-Like Receptor 9 / Q000819:agonists / Q000235:genetics / Q000378:metabolism*; D000099218:Interferon Regulatory Factor-4
chemical_list: D018951:Antigens, CD20; D004268:DNA-Binding Proteins; D050835:Interferon Regulatory Factors; D016328:NF-kappa B; D009838:Oligodeoxyribonucleotides; D051560:Proto-Oncogene Proteins c-bcl-6; D012333:RNA, Messenger; D051217:Toll-Like Receptor 9; D000099218:Interferon Regulatory Factor-4; C084103:BCL6 protein, human; C408982:CPG-oligonucleotide; C495371:TLR9 protein, human