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2024 The John & Daria Barry Foundation – PCF Young Investigator Award in honor of Jason Wilson

Dissecting Myeloid-Mediated Mechanisms of Immunotherapy Resistance in Advanced Prostate Cancer at Single-Cell Resolution

Aram Lyu, PhD
Fred Hutchinson Cancer Center

Mentor: Lawrence Fong, MD

Description:

  • Patients with metastatic castration-resistant prostate cancer (mCRPC) are largely resistant to checkpoint immunotherapy, presenting a significant clinical challenge. Understanding the mechanisms underlying this resistance is critical yet remains largely unmet. 
  • Dr. Aram Lyu is studying the role of immunosuppressive myeloid cells within prostate tumors in oppressing responses to checkpoint immunotherapy, and has identified myeloid cell metabolism as a possible therapeutic target for blocking myeloid cell activity to enhance efficacy of immunotherapy. 
  • This project will investigate the hypothesis that aberrant lipid metabolism in tumor-associated myeloid cells contributes to immunotherapy resistance.
  • The molecular mechanisms underlying the evolution of myeloid-mediated resistance to immunotherapy in prostate cancer will be investigated.
  • Whether targeting dysregulated lipid metabolism can reverse myeloid-mediated immunotherapy resistance during the progression of prostate cancer will be determined.
  • If successful, this project will substantially deepen our understanding of the role dysregulated lipid metabolic processes play in myeloid-mediated immunotherapy resistance, potentially revealing new therapeutic approaches for prostate cancer.

What this means to patients: Checkpoint immunotherapy can be highly effective and even curative in patients with certain cancer types, but rarely has efficacy in prostate cancer. Dr. Lyu’s project will investigate the role of immunosuppressive myeloid cells within prostate tumors in preventing responses to immunotherapy, and determine the potential for blocking myeloid cell metabolism can reverse myeloid-mediated immunotherapy resistance. This could lead to a new therapeutic strategy to greatly increase the efficacy of immunotherapy in patients with prostate cancer.