Saturday, April 26, 2025
4/26/2025
Enhancing the efficacy of radiation by spatially restricting anti-TGFb treatment to the tumor - PROJECT SUMMARY/ABSTRACT Self-renewing stem-like CD8+ T cells (Tstem-like), defined by expression of transcription factor TCF1/LEF, dwell in lymphoid tissues and are critical for anti-tumor immune responses. The role of Tstem-like cells in local and distant radiation response has not been defined. Preliminary single-cell RNA sequencing data demonstrates Tstem-like cells expand to repopulate the tumor within 3 days of radiation. In our first Aim we will determine whether Tstem- like cells from the tumor-draining lymph node are required for radiation response. Radiation and Transforming growth factor beta (TGFβ) inhibition are a promising therapeutic combination. However, TGFβ has opposing effects in anti-tumor CD8+ T cell differentiation, supporting Tstem-like cells in the tumor-draining lymph node, while simultaneously promoting exhaustion of tumor-infiltrating CD8+ T cells. In Aims 2 and 3, we will test radiation with 2nd generation TGFβ targeting therapeutics that spatially restrict the activity to the tumor microenvironment and relatively spare the tumor-draining lymph node, to determine whether spatial restriction of TGFβ inhibition is able to preserve Tstem-like cells and thereby enhance the efficacy of combination therapy.
HHS’ Tracking Accountability in Government Grants System (TAGGS) website provides access to detailed descriptions of grants, loans, aggregated direct payments and other types of financial assistance awarded by the HHS Operating Divisions (OPDIVs) and the Office of the Secretary Staff Divisions (STAFFDIVs).