Mechanisms of Immune Resistance in Advanced Prostate Cancer

Treatment of patients with castration-resistant prostate cancer (CRPC) includes the use of next-generation hormonal therapies such as abiraterone or enzalutamide. Although these therapies are initially effective, a significant proportion of patients exhibit primary or acquired resistance to these treatments. In recent years checkpoint blockade therapies have led to remarkable clinical responses in patients with several tumor types, however, CRPC has remained recalcitrant to immunotherapy. The characterization of tumor resistance mechanisms has led to the identification of various tumor variants that may emerge along the progression of prostate cancer, including tumors undergoing lineage or phenotypic plasticity in the context of an epithelial-mesenchymal transition (EMT). Our laboratory and others have shown that phenotypic plasticity is a driver of resistance to immunotherapy. Based on this knowledge, we investigated whether changes in tumor phenotype could affect the response of CRPC to immune-mediated cytotoxicity and ways to enhance immune-based lysis for potential future combinations of immunotherapy and agents that increase tumor susceptibility to immune attack.

Author

• Dahut, Madeline

Language

• en

Keyword

• Therapy Resistance
• NK-Cell Based Therapy
• Immunotherapy Resistance
• Estrogen Receptor
• Prostate Cancer

Date created

• 2023

Type of Work

• Dissertation

License

• All rights reserved

Rights statement

• In Copyright

GW Unit

• Microbiology & Immunology

Degree

• Ph.D.

Advisor

• Leitenberg, David
• Palena, Claudia

Committee Member(s)

• Chiappinelli, Katherine
• Lee, Norman
• Hodge, James
• Bosque-Pardos, Alberto
• Karzai, Fatima

Persistent URL

•  https://scholarspace.library.gwu.edu/etd/fn106z761