title: Vascular adhesion protein 1 mediates binding of immunotherapeutic effector cells to tumor endothelium.
abstract: Tumor-infiltrating lymphocytes (TIL) can be used as an immunotherapeutic tool to treat cancer. Success of this therapy depends on the homing and killing capacity of in vitro-activated and -expanded TIL. Vascular adhesion protein 1 (VAP-1) is an endothelial molecule that mediates binding of lymphocytes to vessels of inflamed tissue. Here, we studied whether VAP-1 is involved in binding of TIL, lymphokine-activated killer (LAK) cells, and NK cells to vasculature of the cancer tissue. We demonstrated that VAP-1 is expressed on the endothelium of cancer vasculature. The intensity and number of positive vessels varied greatly between the individual specimens, but it did not correlate with the histological grade of the cancer. Using an in vitro adhesion assay we showed that VAP-1 mediates adhesion of TIL, LAK, and NK cells to cancer vasculature. Treatment of the tumor sections with anti-VAP-1 Abs diminished the number of adhesive cells by 60%. When binding of different effector cell types was compared, it was evident that different cancer tissues supported the adhesion of TIL to a variable extent and LAK cells were more adhesive than TIL and NK cells to tumor vasculature. These data suggest that VAP-1 is an important interplayer in the antitumor response. Thus, by up-regulating the expression of VAP-1 in tumor vasculature, it can be possible to improve the effectiveness of TIL therapy.
authors.affiliation: National Public Health Institute and MediCity Research Laboratory, University of Turku, Tykistökatu 6A, FIN-20520 Turku, Finland. heikki.irjala@utu.fi
authors.forename: H
authors.initials: H
authors.lastname: Irjala
authors.forename: M
authors.initials: M
authors.lastname: Salmi
authors.forename: K
authors.initials: K
authors.lastname: Alanen
authors.forename: R
authors.initials: R
authors.lastname: Grénman
authors.forename: S
authors.initials: S
authors.lastname: Jalkanen
mesh_terms: D006631:Amine Oxidase (Copper-Containing) / Q000032:analysis / Q000096:biosynthesis / Q000502:physiology*; D002294:Carcinoma, Squamous Cell / Q000098:blood supply* / Q000737:chemistry / Q000276:immunology* / Q000628:therapy; D002448:Cell Adhesion / Q000276:immunology; D015815:Cell Adhesion Molecules / Q000032:analysis / Q000096:biosynthesis / Q000502:physiology*; D004730:Endothelium, Vascular / Q000737:chemistry / Q000276:immunology* / Q000473:pathology; D006258:Head and Neck Neoplasms / Q000098:blood supply* / Q000737:chemistry / Q000276:immunology* / Q000628:therapy; D006801:Humans; D007150:Immunohistochemistry; D016219:Immunotherapy, Adoptive; D015979:Killer Cells, Lymphokine-Activated / Q000276:immunology / Q000637:transplantation; D007694:Killer Cells, Natural / Q000276:immunology / Q000637:transplantation; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology* / Q000637:transplantation
chemical_list: D015815:Cell Adhesion Molecules; C076668:AOC3 protein, human; D006631:Amine Oxidase (Copper-Containing)