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2024 Eustace Wolfington – PCF Young Investigator Award

Elucidating Drivers of Immune Evasion and Disease Progression in Advanced Prostate Cancer Using Spatial Single-Cell Profiling

William Chen, MD
University of California, San Francisco


Mentors: Felix Feng, MD; Joshua Lang, MD; Bernd Bodemiller, PhD

Description:

  • Tumors are composed of various cell types in addition to cancer cells, including immune and stromal cells, which may contribute to cancer progression and response to androgen signaling inhibitors. However, the interactions and relationships between these cell subtypes remain unclear.
  • Dr. William Chen and team have optimized a custom prostate cancer assay using a specialized technology that profiles individual cells in unprecedented detail. By using pre- vs. post-treatment patient biopsies, this assay can validate cell subtypes and cell-cell interactions driving disease progression and treatment response.
  • In this project, spatial single-cell profiling technologies will be used to determine whether treatment with androgen signaling inhibitors impacts the expression of a key immune activating protein (MHC-I) and immune cell infiltration in tumor biopsies from patients with prostate cancer.
  • A new computational tool will be developed for data analysis of this novel, high-dimensional data type and will be shared with the broad research community.
  • This project will comprehensively investigate immune, stromal, and prostate cancer cells in patient tumors measured before and after standard-of-care treatment and will provide new computational tools for the cancer genomics research community.  

What this means to patients: To comprehensively understand tumor biology and treatment resistance, single-cell resolution-based studies are needed to characterize, quantify, and spatially localize different cell types in tumors. Dr. Chen will apply a new single-cell profiling technique to interrogate prostate cancer tumor biology in the context of treatment resistance. This study will validate the impact of androgen signaling inhibitors on immune responses and identify targetable markers associated with treatment resistance to guide the development of new treatment strategies in advanced prostate cancer.