Head and neck cancer triggers the internalization of TLR3 in natural killer cells.
Natural killer (NK) cells play a dominant role in the network of innate immunity. Via Toll-like receptor 3 (TLR3), NK cells can be efficiently stimulated by double-stranded (ds)RNA. In head and neck squamous cell carcinoma (HNSCC), NK cells seem to be strongly impaired, but the true mechanisms of immune escape are not sufficiently known to date. It is obvious that the microenvironment of head and neck cancer results in strongly affected immune functions. NK cells play a major role in the local immune response of HNSCC. In this study we showed that TLR3 is predominantly expressed on the cell surface of native NK cells and becomes rapidly internalized in response to the HNSCC microenvironment. These findings represent a novel potential immune escape mechanism of head and neck cancer. The internalization of TLR3 in response to HNSCC was also observed in fibroblasts expressing heterologous TLR3 protein. Specific stimulation of NK cell TLR3 with its ligand polyinosinic-polycytidylic acid (Poly I:C) impairs the internalization of this Toll-like receptor and leads to activated NK cells within the HNSCC microenvironment.
Xie
Lei
L
Department of Head and Neck Surgery, Sir Run Run Shaw Hospital, Zhejiang University, 310016 Hangzhou, P.R. China.
Pries
Ralph
R
Kesselring
Rebecca
R
Wulff
Sandra
S
Wollenberg
Barbara
B
D000328:Adult; D000368:Aged; D000818:Animals; D045744:Cell Line, Tumor; D002469:Cell Separation; D004705:Endocytosis / Q000187:drug effects; D005260:Female; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D005434:Flow Cytometry; D006258:Head and Neck Neoplasms / Q000276:immunology* / Q000473:pathology*; D006801:Humans; D007694:Killer Cells, Natural / Q000187:drug effects / Q000276:immunology / Q000378:metabolism* / Q000473:pathology*; D008213:Lymphocyte Activation / Q000187:drug effects; D008297:Male; D051379:Mice; D008875:Middle Aged; D018448:Models, Immunological; D041681:NIH 3T3 Cells; D011070:Poly I-C / Q000494:pharmacology; D021381:Protein Transport / Q000187:drug effects; D013347:Subcellular Fractions / Q000187:drug effects; D051196:Toll-Like Receptor 3 / Q000378:metabolism*