Abstract PO026: Loss of STAT5 in macrophages potentiates tissue remodeling and tumor-promoting phenotype in breast cancer

Abstract

Abstract Despite advances in treating breast cancer, limited targeted therapeutics exist for the triple negative breast cancer (TNBC) subtype, therefore it remains the most fatal relative to other breast cancer subtypes. Since TNBC tumor cells utilize the Janus Kinase (JAK)/Signal Transducer and Activator of Transcription (STAT) pathway for growth and proliferation signals, new therapeutics are being developed to target components of this pathway like STAT5. However, this pathway is also important for infiltrating inflammatory cells such as, macrophages, and their function in the tumor microenvironment. My data indicates that STAT5 is critical for tissue remodeling phenotypes and cell survival in macrophages, which can have a significant impact on tumor progression. I have observed increases in macrophage production of extracellular matrix components when STAT5 signaling is impaired, as well as a localization of STAT5-active macrophages at the tumor border suggesting a role in metastatic restraint. I have also shown that loss of STAT5 in tumor-associated macrophages correlates to an increase in tumor metastases in vivo. The goal of my research is to define the specific functional contributions of STAT5 to macrophage polarization and macrophage-mediated resistance of tumors to JAK/STAT inhibition. To address these questions, my research employs the use of mouse mammary tumor models, clinically-relevant JAK/STAT inhibition and conditional knockout strategies to understand how macrophages can shift from tumor-hostile to tumor-friendly, as well as, provide rationale for potential therapeutic interventions to maintain an anti-tumor response against TNBC. Citation Format: Emily A. Jesser, Kathryn L. Schwertfeger. Loss of STAT5 in macrophages potentiates tissue remodeling and tumor-promoting phenotype in breast cancer [abstract]. In: Proceedings of the AACR Virtual Special Conference on the Evolving Tumor Microenvironment in Cancer Progression: Mechanisms and Emerging Therapeutic Opportunities; in association with the Tumor Microenvironment (TME) Working Group; 2021 Jan 11-12. Philadelphia (PA): AACR; Cancer Res 2021;81(5 Suppl):Abstract nr PO026.