Harnessing Listeria monocytogenes to target tumors

Because of its cytosolic localization, Listeria monocytogenes (LM) has long been considered an attractive tool for delivering tumor-associated antigens (TAA) antigens in vivo to combat cancer. LM directly infects antigen-presenting cells (APC) such as monocytes, macrophages and dendritic cells (DC), thereby delivering the TAA into their cytoplasm, resulting in processing and presentation of the antigen to the immune system. This activates adaptive and innate immune responses to the TAA, mediating tumor cell cytolysis. Recently we discovered additional pathways by which Listeria can be harnessed to induce tumor cell death, which suggest new directions in the development of vaccines or therapies against cancer. In one approach, we have used Listeria to induce immune responses that destroy tumor vasculature. Another new pathway involves selective infection of cancer cells with Listeria, followed by tumor cell death through the production of high levels of reactive oxygen species (ROS) and through Listeria-specific cytotoxic T lymphocytes (CTL). This review will focus on the most recent studies on the multiple pathways of LM and how they can be harnessed in the battle against cancer.