Abstract 3253: Mast cell-derived granzyme b contributes to resistance against anti-angiogenic therapy

Significance: Targeted therapies have revolutionized the treatment of cancer. However, efficacy of anti-angiogenic therapies is limited due to significant resistance. Recent studies showed that the tumor microenvironment is involved in resistance towards targeted anti-angiogenic treatment. Based on the correlation of mast cell (MC) density with tumor growth and angiogenesis we put forward the hypothesis that MC might be implicated in anti-angiogenic therapy resistance. Methods: C57BL/6J, NSG or MC-deficient KitW-sh (Wsh) mice were subcutaneously injected with 5×105 (Panc02 and EL4) or 1×106 (TD2) cells +/- bone marrow derived MC. Tumors were treated with 20 mg/kg anti-VEGFR2 antibody (DC101) or 25 mg/kg cromoglicic acid (Cromo). BrdU was injected 12 h before sacrifice. Results: We show that MC alter the proliferative and organizational state of endothelial cells (EC). MC dose-dependently induced EC-proliferation (158 ± 12%; *p