Vascular adhesion protein 1 mediates binding of immunotherapeutic effectorcells to tumor endothelium

Tumor-infiltrating lymphocytes (TIL) can be used as an immunotherapeutic to ol to treat cancer. Success of this therapy depends on the homing and killi ng capacity of in vitro-activated and -expanded TIL. Vascular adhesion prot ein 1 (VAP-1) is an endothelial molecule that mediates binding of lymphocyt es to vessels of inflamed tissue. Here, we studied whether VAP-1 is involve d in binding of TIL, lymphokine-activated killer (LAK) cells, and NK cells to vasculature of the cancer tissue. We demonstrated that VAP-1 is expresse d on the endothelium of cancer vasculature. The intensity and number of pos itive vessels varied greatly between the individual specimens, but it did n ot correlate with the histological grade of the cancer. Using an in vitro a dhesion assay we showed that VAP-1 mediates adhesion of TIL, LAK, and NK ce lls to cancer vasculature. Treatment of the tumor sections with anti-VAP-1 Abs diminished the number of adhesive cells by 60%. When binding of differe nt effector cell types was compared, it was evident that different cancer t issues supported the adhesion of TIL to a variable extent and LAK cells wer e more adhesive than TIL and NK cells to tumor vasculature. These data sugg est 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 p ossible to improve the effectiveness of TIL therapy.