title: Combined toll-like receptor 3/7/9 deficiency on host cells results in T-cell-dependent control of tumour growth.
abstract: Toll-like receptors (TLRs) are located either on the cell surface or intracellularly in endosomes and their activation normally contributes to the induction of protective immune responses. However, in cancer their activation by endogenous ligands can modulate tumour progression. It is currently unknown how endosomal TLRs regulate endogenous anti-tumour immunity. Here we show that TLR3, 7 and 9 deficiencies on host cells, after initial tumour growth, result in complete tumour regression and induction of anti-tumour immunity. Tumour regression requires the combined absence of all three receptors, is dependent on both CD4 and CD8 T cells and protects the mice from subsequent tumour challenge. While tumours in control mice are infiltrated by higher numbers of regulatory T cells, tumour regression in TLR-deficient mice is paralleled by altered vascular structure and strongly induced influx of cytotoxic and cytokine-producing effector T cells. Thus, endosomal TLRs may represent a molecular link between the inflamed tumour cell phenotype, anti-tumour immunity and the regulation of T-cell activation.
authors.affiliation: Research Division of the Department of Otorhinolaryngology, University Hospital Essen, University Duisburg-Essen, Hufelandstrasse 55, D-45122 Essen, Germany.
authors.forename: Johanna C
authors.initials: JC
authors.lastname: Klein
authors.affiliation: Research Division of the Department of Otorhinolaryngology, University Hospital Essen, University Duisburg-Essen, Hufelandstrasse 55, D-45122 Essen, Germany.
authors.forename: Katrin
authors.initials: K
authors.lastname: Moses
authors.affiliation: Institute of Virology, University Hospital Essen, University Duisburg-Essen, D-45122 Essen, Germany.
authors.forename: Gennadiy
authors.initials: G
authors.lastname: Zelinskyy
authors.affiliation: Research Division of the Department of Otorhinolaryngology, University Hospital Essen, University Duisburg-Essen, Hufelandstrasse 55, D-45122 Essen, Germany.
authors.forename: Simon
authors.initials: S
authors.lastname: Sody
authors.affiliation: Institute of Medical Microbiology, University Hospital Essen, University Duisberg-Essen, D-45122 Essen, Germany.
authors.forename: Jan
authors.initials: J
authors.lastname: Buer
authors.affiliation: Research Division of the Department of Otorhinolaryngology, University Hospital Essen, University Duisburg-Essen, Hufelandstrasse 55, D-45122 Essen, Germany.|German Cancer Consortium (DKTK), D-45122 Essen, Germany.
authors.forename: Stephan
authors.initials: S
authors.lastname: Lang
authors.affiliation: German Cancer Consortium (DKTK), D-45122 Essen, Germany.|Skin Cancer Unit of the Department of Dermatology, West German Cancer Center, University Hospital Essen, University Duisberg-Essen, D-45122 Essen, Germany.
authors.forename: Iris
authors.initials: I
authors.lastname: Helfrich
authors.affiliation: Institute of Virology, University Hospital Essen, University Duisburg-Essen, D-45122 Essen, Germany.
authors.forename: Ulf
authors.initials: U
authors.lastname: Dittmer
authors.affiliation: Institute of Medical Microbiology, University Hospital Essen, University Duisberg-Essen, D-45122 Essen, Germany.
authors.forename: Carsten J
authors.initials: CJ
authors.lastname: Kirschning
authors.affiliation: Research Division of the Department of Otorhinolaryngology, University Hospital Essen, University Duisburg-Essen, Hufelandstrasse 55, D-45122 Essen, Germany.|German Cancer Consortium (DKTK), D-45122 Essen, Germany.
authors.forename: Sven
authors.initials: S
authors.lastname: Brandau
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D011992:Endosomes / Q000378:metabolism; D005260:Female; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009374:Neoplasms, Experimental / Q000276:immunology* / Q000378:metabolism; D013601:T-Lymphocytes / Q000502:physiology*; D051193:Toll-Like Receptors / Q000378:metabolism*; D059016:Tumor Microenvironment
chemical_list: D051193:Toll-Like Receptors