Summary
Immunotherapy is the process of activating a person’s own immune system to attack their cancer. It has been successful in some types of cancers, like melanoma and lung cancer, but little has been done in desmoid tumors. Dr. Gerlinde Wernig will investigate whether desmoid tumors express certain proteins that help it avoid the immune system. These proteins that help tumor cells avoid the immune system are called immune checkpoints and include CD47, PDL1, and CTLA4 (among others). If Dr. Wernig’s group finds these immune checkpoints are expressed on desmoid tumor cells, they will determine if desmoid tumors respond to certain drugs that block these proteins, called immune checkpoint inhibitors. This may lead the way for further research in immunotherapy in desmoid tumors, including possible trials with immunotherapies – several of which are already approved for other cancers.
Scientific Abstract
Desmoid-type fibromatosis (DTF) is a rare, low-grade, soft-tissue tumor affecting the extremities and the trunk. As DTF does not progress after diagnosis in most cases, no specific initial treatment is recommended. However, a minority of patients develop progressive DTF with debilitating and life-threatening complications. In these cases, therapies include chemotherapy, surgery, radiation, or targeted therapy. Immunotherapy either targets immune checkpoints, thereby increasing the efficiency of the adaptive immune system, or don’t-eat-me signals, thereby enhancing the phagocytosis of tumor cells through the innate immune system. Though immunotherapy has significantly increased survival in a variety of cancers, it has not been explored in DTF yet. This is why we propose to investigate whether immunotherapy, more specifically blocking CD47 as a don’t-eat-me-signal, as a potential therapy for DTF. To this end, we will first determine through ATAC Seq if CD47 and immune checkpoint regulatory proteins such as PDL1 are differentially regulated in DTF. Then, we will use a unique adaptive transfer model to explore whether CD47 blockade eliminates ectopic human DTF grafts under the kidney capsule of immunocompromised mice. These results will not only expand knowledge on how don’t-eat-me-signals and immune checkpoints are regulated in DTF but will also explore CD47 blockade as a new therapy for DTF.
