Elina Wells Rose Hills
Using Listeria Monocytogenes to Change the Suppressive State of the Tumor Microenvironment to a Proinflammatory State
Immunosurveillance is the immune system’s ability to detect foreign pathogens, such as bacteria, viruses, and cancerous cells in the body. Many cancers evade immunosurveillance, through the use of mechanisms, which allow them to exist and spread undetected. Checkpoint blockade therapy – an immunotherapy treatment method in part developed at Berkeley – counters the “breaks” of immunosuppressive cells, imposed on inflammatory immune cells within the tumor microenvironment. Many current immunotherapies use Listeria monocytogenes as a way to induce immune cells that were previously exhausted to regain their effector phenotype and control cancer. However, about half of the patients fail to respond to treatment. This may be because immunosuppressive cells within the tumor microenvironment dampen any immune response leading to unresponsive inflammatory cells. I propose that changing the injection method from intravenous (IV) to intratumoral (IT) injection will counter these shortcomings because an immune response will generate directly within the tumor. My research project will use IT injection into both immunogenic and non-immunogenic tumors in a mouse model to address the following questions: Does IT injection combat the challenges presented by IV injection and allow for a greater anti-tumor response, and how can it be optimized?