Abstract 165: Role of SRC-3 in regulatory T cells as a modulator of activation and immunological memory.

Abstract 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. Citation Format: Davis A. Graham, Yan Xia, Subhashree Pradhan, Amrit Koirala, Xiaobin Yu, Adam M. Dean, Bryan C. Nikolai, Aiden L. Moser, Jianming Xu, Cristian Coarfa, Bert W. O'Malley, David M. Lonard. Role of SRC-3 in regulatory T cells as a modulator of activation and immunological memory [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 165.