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2020 James Maguire-PCF VAlor Young Investigator Award

Understanding the Role of Androgen Signaling in Facilitating Immune Evasion in Advanced Prostate Cancer

Lisa Chesner, PhD
University of California, San Francisco

Mentors: Felix Feng, MD; Lawrence Fong, MD; Matthew Cooperberg, MD, MPH

Description:

  • There is an urgent need to improve treatments for patients with advanced prostate cancer. Immunotherapy is one treatment option that has been highly successful in many cancer types but has had limited success in prostate cancer patients. Strategies to improve immunotherapy for prostate cancer are greatly needed.
  • The major histocompatibility complex (MHC) are surface molecules that present antigens to immune cells and are required for T-cell activation. Theoretically, presentation of antigens from mutated proteins by MHC on cancer cells could induce immune responses against the cancer. However, prostate cancer and other cancer types typically downregulate MHC expression in order to evade anti-tumor immune responses.
  • Dr. Lisa Chesner is studying the mechanisms of MHC downregulation in prostate cancer and methods for increasing expression. She hypothesizes that the androgen receptor (AR), the primary driver of prostate cancer, plays a role in MHC downregulation.
  • In this project, Dr. Chesner will determine the biological relationship between AR and MHC levels in prostate cancer cells, including investigating whether AR directly suppresses MHC gene expression.
  • Whether AR-targeted therapies used to treat prostate cancer can increase MHC levels will be investigated.
  • In addition, whether AR-targeted therapy can synergize with checkpoint immunotherapy in the activation of anti-tumor immune responses, will be investigated.
  • If successful, this project will yield insights into how AR regulates MHC and help identify new combination treatments that improve the efficacy of immunotherapy in patients with advanced prostate cancer.

What this means to patients: Dr. Chesner is investigating whether levels of MHC, which are proteins required for anti-tumor immune responses, are suppressed in prostate cancer via AR. This project will also reveal whether AR-targeted therapy may synergize with immunotherapy and could lead to new therapeutic strategies for patients with prostate cancer.