Aria Sokol
Research Mentor: Cody Hager
Mentor Department: Hematology/Oncology, Medicine
Author(s): Aria Sokol, Cody Hager, Deeksha Sharma, Monika Burness
Session: Session 7 (4:00 PM – 4:50 PM)
Presentation Type: Poster 85
Abstract
Background: The tumor microenvironment (TME) is a major contributor to breast cancer’s ability to resist immunotherapies by suppressing T-cell function and promoting exhaustion in the TME. Cancer-associated fibroblasts (CAFs) and tumor-associated macrophages (TAMs) are key mediators of immune suppression through inhibitory signaling and immune exclusion. Bromodomain and extra-terminal (BET) proteins regulate transcriptional programs, including those involved in immune exclusion. We investigated whether targeting BET proteins using ZBC260, a potent BET degrader, could influence these immune processes. We hypothesize that BET-targeting therapies, such as ZBC260, help reshape the immune landscape to enhance T-cell function, overcoming immune suppression. Methods: Jurkat T-cells, a human T-cell leukemia cell line, were treated with increasing concentrations of ZBC260 and assessed for viability using CellTiter-Glo assays every 24 hours up to 5 days. Protein expression of BET family members (BRD2, BRD3, and BRD4), and the downstream oncogenic target MYC, were assessed by Western blot following 3 days of ZBC260 treatment. Results: ZBC260 treatment resulted in a dose and time dependent decrease in T-cell viability. Consistent with BET degradation, ZBC260 decreased expression of BET proteins and the downstream target MYC. Conclusion: Overall, this study highlights the potential of BET degradation to influence immune regulation within the tumor microenvironment. While reduced T-cell viability was observed, ongoing studies aim to determine how BET degradation influences T-cell function and interactions with immunosuppressive cell populations such as TAMs and CAFs within the TME to influence tumor growth. Further studies may inform therapeutic strategies aimed at improving anti-tumor immune responses in breast cancer.
