> Our Work > The Work We Fund

2025 Igor Tulchinsky – PCF Young Investigator Award

Loss of the Y Chromosome as a Driver of Tumor Aggressiveness and Novel Biomarker for Immunotherapeutic Response in Prostate Cancer

Timothy Gauntner, DO, PhD
Ohio State University

Mentors: Zihai Li; Steven Clinton; Qin Ma

Description:

  • Prostate cancer is characterized by an immunosuppressed tumor microenvironment, limiting the efficacy of immunotherapies like Sipuleucel-T. There is a critical need for predictive biomarkers to identify patients likely to respond to Sipuleucel-T and other therapies such as 177-lutetium-PSMA (LuPSMA) or docetaxel.
  • Tumor-specific Loss of Y chromosome (LOY), observed in 5-30% of prostate cancer cases, has been linked to tumor aggressiveness and immune suppression. Recent work demonstrated that LOY promotes an immunosuppressive tumor microenvironment in bladder cancer and enhances response to immune checkpoint inhibitors, suggesting a similar role in prostate cancer.
  • Dr. Timothy Gauntner hypothesizes that LOY in prostate cancer drives tumor aggression through immune evasion and resistance to chemo and radiotherapies while sensitizing tumors to immunotherapies like Sipuleucel-T and immune checkpoint inhibitors.
  • In this project, Dr. Gauntner will characterize LOY’s role in prostate cancer, identify potential LOY-driven immune evasion pathways, and determine LOY-based biomarkers to predict responses to therapies including Sipuleucel-T, docetaxel, and LuPSMA.
  • If successful, this study will provide mechanistic insights into how LOY drives prostate cancer aggressiveness and therapy response, potentially leading to novel LOY-based biomarkers and clinical trials testing new LOY immune evasion-targeting therapies that could transform prostate cancer treatment paradigms.

What this means to patients: Loss of Y chromosome (LOY) is observed in up to 30% of prostate cancer cases, and may impact tumor biology, anti-tumor immune activity, and responses to therapies. Dr. Gauntner’s project will define the role of LOY in prostate cancer and immune responses, and determine whether LOY predicts responses to various therapies, including immunotherapies. This could lead to new biomarkers for selecting optimal treatments for individual patients, and provide rationale for testing new immunotherapies in patients with LOY tumors.