Samuel Lucas
BME PhD Defense Presentation

Date: 2025-11-10
Time: 2:00 PM - 4:00 PM
Location / Meeting Link: UAW McIntire Conference Room / Zoom: https://gatech.zoom.us/j/99454679695?pwd=UFvAEeotLy0zQLxpIa0CsdlHSmBVO0.1

Committee Members:
Susan Thomas, PhD (Advisor); Brandon Dixon, PhD; Edward Botchwey, PhD; M.G. Finn, PhD; Haydn Kissick, PhD;


Title: Engineering T Cell Response to Immunotherapy in Tumor Draining Lymph Nodes

Abstract:
Despite significant advances in cancer immunotherapy since the approval of the first generation of immune checkpoint blockade (ICB) therapies, a majority of immunotherapy-eligible cancer patients do not experience significant therapeutic benefit. Efforts to improve patient outcomes have illuminated many of the complexities of T cell biology and how those complexities influence response to immunotherapy. Most attempts to modulate T cell immunity in the context of immunotherapy have focused on the tumor microenvironment (TME). Yet, the role played in immunotherapeutic response by tumor-draining lymph nodes (TDLNs), the tissues in which most antitumor T cell priming occurs as a result of interactions between naïve T cells and tumor antigen-accessing antigen presenting cells (APCs), has been generally underappreciated. To address this shortfall, it is necessary to further investigate how immunomodulation in TDLNs alters T cell response to immunotherapy. The research presented herein uses engineered biomaterials to deliver adjuvant to TDLN APCs, probing how TDLN APC modulation influences the quality, magnitude, and dynamics of both local and systemic T cell immunity during ICB. Questions explored with this approach include how sustained adjuvant delivery to the TDLN alters the potency and duration of T cell immunity and what role dendritic cell (DC) tissue residency plays in T cell response. This work also applies an in situ cell tracking system to demonstrate that both locally and systemically administered immunotherapies, rather than exclusively acting upon T cells already within the TME, in fact prompt T cells to mobilize from the TDLN and migrate to the TME. It is anticipated that the insights obtained in the course of this research will ultimately inform more effective cancer immunotherapy strategies specifically tailored to take advantage of the unique capacity of TDLNs to guide antitumor immunity.