Michelle L. Bookstaver, PhD, CRI-Bristol Myers Squibb Postdoctoral Fellow Brigham & Women's Hospital Our immune system is designed to recognize and eliminate cancer cells through the same mechanisms as it would with invading pathogens. CD8+ T cells in particular recognize atypical cancer antigens presented on the surface of antigen presenting cells (APCs) that instruct them to destroy cancer cells. However, tumors have developed mechanisms to evade the immune system by “turning off” the CD8+ T cell attack. CD8+ T cells that invade the tumor are known to lose functionality and develop dysfunctional or “exhausted” phenotypes as tumors progress, thereby resulting in their inability to eliminate the tumor. The emergence of immunotherapies, which are designed to stop tumor cells from “turning off” CD8+ T cells, has made a significant impact in the cancer field. However, these therapies are only successful in a fraction of cancer patients and do not work for all cancer types. Thus, there is an urgent need for novel immunotherapy strategies. Dr. Bookstaver’s work has identified molecules that mediate interactions between APCs and CD8+ T cells that decrease during tumor progression. In this proposal, Dr. Bookstaver will test how modulation of these molecules impacts the anti-tumor functions of CD8+ T cells and will test two different therapeutic approaches to improve the interaction between APCs and CD8+ T cells using cell engineering and engineered nanoparticles. The goal is to understand how interaction with APCs regulate the functions of CD8+ T cells in cancer and to leverage this information to design novel therapeutic approaches that can be readily translated to the clinic. Dr. Bookstaver is supported by the CRI Irvington Postdoctoral Fellowship to Promote Racial Diversity. Projects and Grants Investigating dynamic cell-cell interactions that determine CD8+ T cell functionality during tumor progression Brigham and Women’s Hospital / Harvard Medical School | All Cancers | 2022 | Ana C. Anderson, Ph.D.