title: Distinct expression patterns of Toll-like receptor 7 in tumour cells and fibroblast-like cells in oral squamous cell carcinoma.
abstract: OBJECTIVE
  Toll-like receptor (TLR)-7 agonists have been used in cancer immunotherapy, but tumour heterogeneity means that TLR-7 activity is variable in different components of the tumour microenvironment and the characteristics of TLR-7 in oral squamous cell carcinoma (OSCC) are unclear.
  
  
  RESULTS
  Twenty healthy oral tissues, 50 oral leukoplakia tissues and 166 retrospective primary OSCC samples were collected for immunohistochemical staining of TLR-7 and showed up-regulated expression during carcinogenesis. Moreover, patients with high expression of TLR-7 in tumour cells (TCs) had poor differentiation and prognosis. Interestingly, patients with high expression of TLR-7 in stroma fibroblast-like cells (FLCs) had low tumour stage, no lymph node metastasis (LNM) and better prognosis. Furthermore, Ki-67, CD3, CD4, CD8 and forkhead box protein 3 (FoxP3)(+) tumour-infiltrated lymphocytes were assessed and we found that TLR-7(high) TCs were infiltrated by fewer CD3(+) CD4(+) but more FoxP3(+) lymphocytes. Importantly, patients with TLR-7(low) TCs and TLR-7(high) FLCs had less FoxP3(+) lymphocyte infiltration and longer survival time than those with TLR-7(high) TCs/TLR-7(low) FLCs, although TLR-7 was not an independent prognostic factor for OSCC.
  
  
  CONCLUSIONS
  The low expression of TLR-7 in tumour and high expression of TLR-7 in stroma predict a good clinical outcome for OSCC patients, and stroma FLCs might be amenable to immunotherapy by a TLR-7 agonist.
authors.affiliation: Nanjing Stomatological Hospital, Medical School and The State Key Laboratory of Pharmaceutical Biotechnology, Division of Immunology, Nanjing university, Nanjing, China.
authors.forename: Yan Hong
authors.initials: YH
authors.lastname: Ni
authors.affiliation: Nanjing Stomatological Hospital, Medical School and The State Key Laboratory of Pharmaceutical Biotechnology, Division of Immunology, Nanjing university, Nanjing, China.
authors.forename: Liang
authors.initials: L
authors.lastname: Ding
authors.affiliation: Nanjing Stomatological Hospital, Medical School and The State Key Laboratory of Pharmaceutical Biotechnology, Division of Immunology, Nanjing university, Nanjing, China.
authors.forename: Dong Ya
authors.initials: DY
authors.lastname: Zhang
authors.affiliation: Nanjing Stomatological Hospital, Medical School and The State Key Laboratory of Pharmaceutical Biotechnology, Division of Immunology, Nanjing university, Nanjing, China.
authors.forename: Ya Yi
authors.initials: YY
authors.lastname: Hou
authors.affiliation: Nanjing Stomatological Hospital, Medical School and The State Key Laboratory of Pharmaceutical Biotechnology, Division of Immunology, Nanjing university, Nanjing, China.
authors.forename: Xiaofeng
authors.initials: X
authors.lastname: Huang
authors.affiliation: Nanjing Stomatological Hospital, Medical School and The State Key Laboratory of Pharmaceutical Biotechnology, Division of Immunology, Nanjing university, Nanjing, China.
authors.forename: Qingang
authors.initials: Q
authors.lastname: Hu
mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis*; D002294:Carcinoma, Squamous Cell / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D018572:Disease-Free Survival; D005260:Female; D005347:Fibroblasts / Q000378:metabolism / Q000473:pathology; D006258:Head and Neck Neoplasms / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D016246:Lymphocytes, Tumor-Infiltrating / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D000077195:Squamous Cell Carcinoma of Head and Neck; D017154:Stromal Cells / Q000378:metabolism / Q000473:pathology; D051199:Toll-Like Receptor 7 / Q000032:analysis / Q000096:biosynthesis*; D059016:Tumor Microenvironment / Q000502:physiology
chemical_list: D014408:Biomarkers, Tumor; C495348:TLR7 protein, human; D051199:Toll-Like Receptor 7
keywords: OSCC; TLR-7; fibroblast-like cells; prognosis; tumour-infiltrated lymphocytes