title: Expression of a single, viral oncoprotein in skin epithelium is sufficient to recruit lymphocytes.
abstract: Established cancers are frequently associated with a lymphocytic infiltrate that fails to clear the tumour mass. In contrast, the importance of recruited lymphocytes during premalignancy is less well understood. In a mouse model of premalignant skin epithelium, transgenic mice that express the human papillomavirus type 16 (HPV16) E7 oncoprotein under a keratin 14 promoter (K14E7 mice) display epidermal hyperplasia and have a predominant infiltrate of lymphocytes consisting of both CD4 and CD8 T cells. Activated, but not naïve T cells, were shown to preferentially traffic to hyperplastic skin with an increased frequency of proliferative CD8+ T cells and CD4+ T cells expressing CCR6 within the tissue. Disruption of the interaction between E7 protein and retinoblastoma tumour suppressor protein (pRb) led to reduced epithelial hyperplasia and T cell infiltrate. Finally, while K14E7 donor skin grafts are readily accepted onto syngeneic, non-transgenic recipients, these same skin grafts lacking skin-resident lymphocytes were rejected. Our data suggests that expression of a single oncoprotein in the epidermis is sufficient for lymphocyte trafficking (including immunosuppressive lymphocytes) to premalignant skin.
authors.affiliation: The University of Queensland Diamantina Institute, University of Queensland, Princess Alexandra Hospital, Woolloongabba, Brisbane, Australia.
authors.forename: Allison
authors.initials: A
authors.lastname: Choyce
authors.forename: Michelle
authors.initials: M
authors.lastname: Yong
authors.forename: Sharmal
authors.initials: S
authors.lastname: Narayan
authors.forename: Stephen R
authors.initials: SR
authors.lastname: Mattarollo
authors.forename: Amy
authors.initials: A
authors.lastname: Liem
authors.forename: Paul F
authors.initials: PF
authors.lastname: Lambert
authors.forename: Ian H
authors.initials: IH
authors.lastname: Frazer
authors.forename: Graham R
authors.initials: GR
authors.lastname: Leggatt
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002452:Cell Count; D004848:Epithelium / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D005786:Gene Expression Regulation; D052162:Human papillomavirus 16; D006965:Hyperplasia / Q000276:immunology / Q000378:metabolism; D007108:Immune Tolerance; D051379:Mice; D050725:Papillomavirus E7 Proteins / Q000737:chemistry / Q000378:metabolism*; D016160:Retinoblastoma Protein / Q000378:metabolism; D012867:Skin / Q000166:cytology / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D059016:Tumor Microenvironment / Q000276:immunology
chemical_list: D050725:Papillomavirus E7 Proteins; D016160:Retinoblastoma Protein; C059731:oncogene protein E7, Human papillomavirus type 16