Targeting SOX11-FAK-Mediated Immune Exhaustion in NF1-Associated Malignant Peripheral Nerve Sheath Tumor (MPNST)
Abstract
Malignant peripheral nerve sheath tumor (MPNST) is a highly aggressive form of cancer that is the leading cause of early death in persons with neurofibromatosis type 1 (NF1). These tumors are highly resistant to treatment due to their ability to escape destruction by the immune system. We have discovered a protein, SOX11, that becomes highly expressed in MPNST and that we believe is critical for allowing tumor cells to hide from immune attack. In this proposal, we will determine the impact of SOX11 on key factors required by the immune system to recognize and destroy human MPNST cells. Additionally, we will establish whether genetic deletion of Sox11 in mice that develop MPNST can prevent tumor growth by promoting anti-tumor immune responses. In other forms of human cancer, SOX11 has been shown to act through a protein called focal adhesion kinase (FAK) to shut down anti-tumor immunity. Defactinib is a drug that blocks the activity of FAK and is already being used in clinical trials to treat patients with other types of cancer. We will determine whether defactinib can reduce the growth of MPNST in mice by enhancing the ability of the immune system to attack and destroy the tumor cells. These studies will enhance our understanding of immune escape pathways in MPNST and, furthermore, have strong potential to justify clinical trials of drugs such as defactinib that block FAK activity in MPNST where no effective treatments currently exist.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Jan 04, 2024
- Source ID
- HT94252310143
Entities
People
- Steven D Rhodes
Organizations
- Indiana University
- United States Army