Exosomal Mirtrons: A Novel Immunosuppressive Mechanism in Breast Tumor Stem Cell 9418

Abstract Description Tumor immune evasion is a critical barrier to effective cancer treatment, particularly in breast cancer stem cells (BTSCs). These resilient cells influence the tumor microenvironment (TME) through intercellular communication, altering immune responses to promote tumor progression. In this study, we identify a novel subclass of small RNAs, mirtrons, secreted via exosomes from BTSCs upon exposure to anti-tumor T lymphocytes. The impact of the mirtrons on breast cancer progression is two-fold, regulation tumor immunity and tumor progression. Upon uptake, mirtrons reduce T cell survival and suppress cytokine secretion such as interferon-gamma and interlukin-2, impairing anti-tumor immunity. Beyond immune suppression, mirtron overexpression in bulk breast cancer cells enhances proliferation and increases Oct4 expression, a key cancer stemness marker. This suggests mirtrons not only suppress immune responses but also reinforce tumor progression and cancer stem cell maintenance. Given their dual role, mirtrons emerge as a potential target for immunotherapy. Understanding mirtron-mediated T cell suppression opens new avenues for therapeutic intervention. Targeting this pathway could enhance T cell efficacy against BTSCs, overcoming a key immune resistance mechanism in breast cancer. This study highlights the significance of mirtrons in tumor-immune interactions and their potential as immunotherapeutic targets. Funding Sources NIGMS GM153648-01 Topic Categories Tumor Immunology: Cellular Responses and Tumor Microevironment (TIME)