Challenge in cancer therapy with VAP-1 inhibition strategy: possible interference of this type of intervention within protection from autoimmunity: Hypothesis

Vascular adhesion protein-1 (VAP-1) is an endothelial cell surface-expressed oxidase involved in leukocyte traffic. The adhesive function, and therefore leukocyte infiltration to different tissues, can be blocked by anti-VAP-1 antibodies as well as small molecule VAP-1 inhibitors. Several papers have been published on the effect of VAP-1 blockade on both leukocyte accumu- lation into tumors and neoangiogenesis. Additionally, myeloid derived suppressor cells (MDSCs) have been identified as immunosuppressive cells associated with tumor expansion. Moreover, some of them (such as CD11b+ myeloid cells) appear to be intrinsically suppressive and may have a key role in maintaining immune homeostasis and protection from autoimmunity. Since VAP-1 supports leukocyte emigration (including MDSCs) to normal tissues and sites of inflammation like tumor tissue, its inhibition has been suggested as potential cancer immunotherapy intervention. Moreover, since these types of suppressive cells use VAP-1 mediated strategy for their adhe- sion and infiltration, it is hypothesized that VAP-1 inhibition may lead to partial loss of suppressive function on immune system and therefore induce the development of autoimmune diseases like relapsing-remitting (experime- ntal) autoimmune encephalomyelitis.