Identification of Siglec-9 Ligand for T-Cell Immunoevasion in Advanced Prostate Cancer
Abstract
Cancer immunotherapy has made tremendous strides in improving the quality and quantity of the life of cancer patients. Unfortunately, immunotherapy remains largely ineffective against advanced prostate cancer. We hypothesize that prostate cancer cells coat themselves in a sugar-modified protein that allows them to evade the immune system. These sugarcoated proteins interact with Siglec proteins on the surface of immune cells and inhibit their ability to fight cancer. We aim to identify which sugar-modified proteins are responsible for immune evasion in prostate cancer. To achieve this goal, we will use advanced analytical methods to study the sugar-modified protein expression on prostate cancer cells and explore their effect on immune inhibition. We will also identify genes for sugar-modified proteins and those that change the sugars using cutting-edge CRISPRi technology. If successful, our work could lead to the development of a new class of drugs that block the sugarcoated proteins from interacting with immune cells. This would be a new paradigm in immunotherapeutic strategies combating aggressive prostate cancers. The proteins identified in this study could also be used as biomarkers to diagnose cancer at early stage or identify aggressive cancers. This study is well aligned with FY20 PCRP Overarching Challenge to improve patients’ quality of life and develop therapeutic treatments for metastatic or aggressive prostate cancer to reduce the deaths. The new class of immunotherapeutic drugs targeting sugar-protein interactions is particularly beneficial to patients with advanced prostate cancer since this study will be carried out on cancer models derived from patients with advanced metastatic prostate cancer. Importantly, this project will also serve as a training vehicle for me to become an academic scientist working in prostate cancer. Our research will lay the foundation to a patient-related clinical trial demonstrating the efficacy of sugar-protein targeting therapeutic drugs in advanced prostate cancer. We expect 5-10 years of laboratory studies before progressing to a patient-related clinical trial. My career goal is to become an independent faculty/scientist focusing on prostate cancer research. The PCRP Young Investigator Award provides me a chance to expand my skills about experiment, project management, personnel management, public speaking, grant and manuscript writing, and mentoring. I will expand my knowledge of cancer genomics, immunology, and clinical aspects on prostate cancer through campus seminars, workshops, courses, and formal and informal interactions with clinicians and scientists. I will have a strong support team with my mentor, Dr. James D. Brooks, a leading clinician-scientist specializing in prostate cancer, and co-mentor, Dr. Sharon Pitteri, who specializes in glycobiology and cancer cell surface proteins. I will frequently meet with Dr. Brooks and Dr. Pitteri to discuss my research projects and possible challenges through weekly individual meetings, formal group meetings, and informal meetings and talks. The mentorship support that I receive will ensure the success of this study and that the findings are clinically relevant. My goal is to make discoveries that will eventually benefit patients with advanced prostate cancer by improving their survival and thereby reducing deaths.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Dec 05, 2021
- Source ID
- W81XWH2110195
Entities
People
- Ru Wen
Organizations
- Stanford University
- United States Army