title: Lymphatic Vessels, Inflammation, and Immunity in Skin Cancer.
abstract: Skin is a highly ordered immune organ that coordinates rapid responses to external insult while maintaining self-tolerance. In healthy tissue, lymphatic vessels drain fluid and coordinate local immune responses; however, environmental factors induce lymphatic vessel dysfunction, leading to lymph stasis and perturbed regional immunity. These same environmental factors drive the formation of local malignancies, which are also influenced by local inflammation. Herein, we discuss clinical and experimental evidence supporting the tenet that lymphatic vessels participate in regulation of cutaneous inflammation and immunity, and are important contributors to malignancy and potential biomarkers and targets for immunotherapy.
  
  
  CONCLUSIONS
  The tumor microenvironment and tumor-associated inflammation are now appreciated not only for their role in cancer progression but also for their response to therapy. The lymphatic vasculature is a less-appreciated component of this microenvironment that coordinates local inflammation and immunity and thereby critically shapes local responses. A mechanistic understanding of the complexities of lymphatic vessel function in the unique context of skin provides a model to understand how regional immune dysfunction drives cutaneous malignancies, and as such lymphatic vessels represent a biomarker of cutaneous immunity that may provide insight into cancer prognosis and effective therapy.
authors.affiliation: Department of Cell, Developmental and Cancer Biology, Oregon Health and Science University, Portland, Oregon. Department of Molecular Microbiology and Immunology, Oregon Health and Science University, Portland, Oregon. Department of Dermatology, Oregon Health and Science University, Portland, Oregon. Knight Cancer Institute, Oregon Health and Science University, Portland, Oregon. lunda@ohsu.edu.
authors.forename: Amanda W
authors.initials: AW
authors.lastname: Lund
authors.affiliation: Department of Cell, Developmental and Cancer Biology, Oregon Health and Science University, Portland, Oregon.
authors.forename: Terry R
authors.initials: TR
authors.lastname: Medler
authors.affiliation: Department of Dermatology, Oregon Health and Science University, Portland, Oregon. Knight Cancer Institute, Oregon Health and Science University, Portland, Oregon.
authors.forename: Sancy A
authors.initials: SA
authors.lastname: Leachman
authors.affiliation: Department of Cell, Developmental and Cancer Biology, Oregon Health and Science University, Portland, Oregon. Knight Cancer Institute, Oregon Health and Science University, Portland, Oregon.
authors.forename: Lisa M
authors.initials: LM
authors.lastname: Coussens
mesh_terms: D014408:Biomarkers, Tumor / Q000276:immunology; D006801:Humans; D042601:Lymphatic Vessels / Q000276:immunology* / Q000473:pathology; D012878:Skin Neoplasms / Q000276:immunology / Q000473:pathology*; D059016:Tumor Microenvironment
chemical_list: D014408:Biomarkers, Tumor