Abstract A044: Kaiso regulates the suppressive immune TME in TNBC

Breast cancer (BCa) remains the most diagnosed cancer in women and one of the leading causes of cancer-related mortality. Triple-negative breast cancer (TNBC), a clinically aggressive subtype defined by the absence of estrogen receptor (ER), progesterone receptor (PR), and HER2 expression, lacks targeted therapeutic options and is associated with poor outcomes. Our lab previously identified the POZ-ZF transcription factor Kaiso (ZBTB33) as a key driver of epithelial–mesenchymal transition (EMT) and metastasis in TNBC via its regulation of E-cadherin expression. However, Kaiso’s role in modulating the immune tumor microenvironment (TME) remains underexplored. Emerging evidence from our lab indicates that Kaiso regulates TGF-β signaling, a critical pathway involved in immune evasion. We have found that Kaiso-expressing TNBC cells preferentially polarize macrophages toward a suppressive M2 phenotype, while Kaiso knockdown reprograms macrophages into a pro-inflammatory M1 state. Patient-derived tumor samples further support this, showing enrichment of regulatory T cells (Tregs), elevated suppressive cytokines, and increased expression of immune checkpoint molecules in Kaiso-high tumors. Through a combination of ELISA, in vitro co-culture models, immunohistological staining of patient tissues, and functional immune assays, we aim to elucidate Kaiso’s role as a central regulator of immune suppression in TNBC. These studies will establish Kaiso as a potential therapeutic target for reversing immune evasion and enhancing the efficacy of immunotherapies in this difficult-to-treat breast cancer subtype. Citation Format: Malik McRae, Ezekiel Wamble, Clayton Yates, Huixian Lin. Kaiso regulates the suppressive immune TME in TNBC [abstract]. In: Proceedings of the 18th AACR Conference on the Science of Cancer Health Disparities; 2025 Sep 18-21; Baltimore, MD. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2025;34(9 Suppl):Abstract nr A044.