Lindsay K. Dickerson, MD, CRI-Fibrolamellar Cancer Foundation Fellow University of Washington Fibrolamellar carcinoma (FLC) is a rare liver cancer affecting children and young adults without underlying liver disease. Patients often present with large tumors and metastases. Surgical resection is the cornerstone of treatment and offers the best chance of cure, however recurrence rates are as high as 90%. Given this high recurrence and metastasis rate, as well as ineffective systemic treatment options, there has been a growing interest in immunotherapy—harnessing patients’ immune systems to fight the cancer. Certain characteristics of the tumor environment and immune response in FLC indicate the immune system is suppressed. First, immune cells are sequestered away from cancer cells. Second, cytotoxic T cells—immune cells that can recognize and kill cancer—are dysfunctional. However, blocking key elements in immune pathways reinvigorates T cell antitumor activity and increases cancer cell killing. Third, receptors on T cells do not multiply as much as in other tumor types suggesting the immune system is not responding normally to immune triggers called antigens. Dr. Dickerson’s project aims to investigate how immunotherapy alters each of these characteristics and thus may be employed to reverse the immune system suppression in FLC. She will first visualize distribution of immune cells in relationship to cancer cells before and after immunotherapy. Next she’ll use slices of FLC tumor to test how combinations of immunotherapy affect cancer cell killing. Finally, she will assess the impact of immunotherapy on T cell receptor multiplication. The ultimate goal is to discover immune system-based treatments that can prolong survival in—or cure—FLC. Projects and Grants Therapeutic modulation of tumor-infiltrating T cell function in fibrolamellar carcinoma University of Washington | Liver Cancer | 2022 | Venu Pillarisetty, MD, and Kevin C. Barry, PhD
