Adam Blaisdell, MD, PhD, Samuel and Ruth Engelberg Postdoctoral Fellow University of California, San Francisco Area of Research: All Cancers Immunotherapy has been revolutionizing cancer treatment for more than a decade. The idea for these therapies came from the field of autoimmunity, wherein it is recognized that certain molecules are designed to suppress immunity. Later it was discovered that cancers take advantage of these molecules to suppress the anti-cancer immune response. By targeting these molecules with immunotherapy, the body’s immune cells are unleashed to attack the growing cancer. Unfortunately, many cancer patients develop resistance to immunotherapy, as cancers acquire mutations to thwart immune cells, while the immune cells within the tumor become exhausted and ineffective. Therefore, there is a need for new approaches to circumvent this resistance. Dr. Blaisdell revisited the autoimmunity paradigm and identified the molecule A20 as a prime target for immunotherapy. While A20 plays a crucial role in preventing autoimmune disease, Dr. Blaidsell’s preliminary data unequivocally shows that cancers use A20 to their own benefit. By inhibiting A20 in mouse models of colon cancer and melanoma, cancer growth is profoundly suppressed. Dr. Blaisdell further narrowed down the key immune cell type and signaling pathway responsible for this suppression and found that A20 inhibition remarkably does not succumb to the aforementioned cancer resistance. His proposal aims to further investigate the signaling pathways responsible, and how A20 inhibition makes immune cells superior cancer killers. Dr. Blaisdell expects his findings will lay the groundwork for A20 inhibition as a first-in class immunotherapy, while also revealing multiple additional novel targets for successful cancer treatment. Projects and Grants A20 in cancer immunity and regulation of CD8 T cell function and fate University of California, San Francisco | All Cancers | 2023 | Averil Ma, M.D.