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Texas Tech University

URC 2023 Abstract

Nicholas Pascuzzi

Exosomal Mirtrons: A Novel Mechanism of Immune Suppression in Breast Tumor Stem Cells

Immune evasion remains a major challenge in breast cancer treatment, particularly in breast tumor stem cells (BTSCs), which modulate the tumor microenvironment (TME) to suppress anti-tumor immune responses. In this study, we identify a novel class of small RNAs, mirtrons, that are secreted via exosomes from BTSCs in response to anti-tumor T lymphocytes. These mirtrons play a dual role in breast cancer progression by regulating tumor immunity and promoting tumor growth. Upon uptake by T cells, mirtrons reduce cell survival and inhibit the secretion of key cytokines, including interferon-gamma and interleukin-2, thereby impairing anti-tumor immune responses. Additionally, mirtron overexpression in bulk breast cancer cells enhances proliferation and upregulates Oct4, a critical stemness marker, suggesting their role in sustaining cancer stem cell properties. Given their immunosuppressive and tumor-promoting functions, mirtrons represent a promising target for immunotherapy. Understanding the mechanisms by which mirtrons mediate T cell suppression could lead to novel therapeutic strategies aimed at enhancing T cell efficacy against BTSCs, addressing a critical barrier in breast cancer treatment. This study underscores the significance of mirtrons in tumor-immune interactions and highlights their potential as therapeutic targets in breast cancer.

Presenter: 312

Nicholas Pascuzzi Senior College of Arts & Sciences Texas Tech University Affiliations: TrUE Project/Travel Funding Recipient; TrUE Scholars Matador

Abstract: C312

Impact Area: Health

Session: C - Wed. April 2, 10:00 AM, TTU Museum Sculpture Garden

Project Author(s)

Nicholas Pascuzzi, Kuan-Hui E. Chen

Mentor

Kuan Hui Chen Biological Sciences TTU College of Arts & Sciences