Role of SRC-3 in regulatory T cells as a modulator of activation and immunological memory

While Steroid Receptor Coactivator 3 (SRC-3) is best known for its role in promoting proliferation of breast cancer cells, our group has recently identified a key role for SRC-3 in regulatory T cells (Tregs). Treg specific knockout (KO) of SRC-3 results in the long-term eradication of primary tumors in a syngeneic model of triple negative breast cancer. SRC-3 KO Treg mice also can resist rechallenge with a second dose of tumor cells. This long-term anti-tumor immunity points to the potential that SRC-3 KO Treg cells are differentiating into T memory cells. Our data shows that SRC-3 KO Tregs express higher levels of the T memory cell markers CD44 and CD62L than wild type Tregs and that SRC-3 KO Tregs downregulate inducible T-cell co-stimulator (ICOS), c-MAF, and interleukin 10 (IL-10). Utilizing single cell multiome sequencing and subsequent functional assays, we aim to further delineate the role of SRC-3 in Tregs and the impact of SRC-3 KO Tregs on the broader effector immune system. Through these assays we will gain insight into the role that SRC-3 has on T memory cell formation and function and the impact of SRC-3 KO Tregs on other immune cells. This work aims to provide a mechanistic delineation of the long term anti-tumor effects of SRC-3 KO Tregs.