Targeting myeloperoxidase (MPO) for multiple myeloma immunotherapy

Lucas Wang St. Joseph Catholic Secondary School Sun Life Gene Medical Science Institute, Cancer Research Program Student, Toronto, Ontario, Canada.

Summary  Among dysregulated functions within the tumour microenvironment, oxidative and inflammatory functions play a critical role in tumour development. One such protein that has both pro-oxidative and proinflammatory properties is MPO. It is primarily expressed in myeloid cells as an oxidative antimicrobial agent but has most recently been found within the bone marrow tumour microenvironment. Its properties make it a promising target for the regulation of the development of cancers such as MM. It was discovered that MM expression and tumour cell homing increased towards areas with elevated myeloid cell expression and MPO activity. Methodically MPO was able to express critical MM growth factors and suppress immune response through reduction in cytotoxic T-cell activity. Therefore finding an inhibitor for MPO is a potentially viable method for preventing the development of MM. The irreversible MPO inhibitor 4-ABAH (4-aminobenzoic Acid Hydrazide) administered in small concentrations was found to reduce the MM tumour burden on affected mice. In short, the collected data show that MPO contributed to the development of tumour growth and that MPO specific inhibitors can serve as potential pharmaceutical strategies to limit MM disease progression.