University of Chicago Researchers Identify Key to Overcoming Immunotherapy Resistance in Prostate Cancer
CHICAGO, IL – May 15, 2024 – A groundbreaking study from teh University of Chicago’s Cancer Center has revealed a mechanism by which prostate cancer evades immunotherapy, offering a potential pathway to improve treatment outcomes for patients who currently don’t respond. Researchers discovered that in non-responsive patients, the immune system inadvertently fuels tumor growth by attracting PD-1 expressing tumor-associated macrophages to the tumor microenvironment.
The research, led by Associate Professor Akash Patnaik, MD, PhD, program leader for the Clinical and Experimental Therapeutics Program, and senior author Dr. Thomas Gajewski, was published May 14, 2024, in Clinical Cancer Research. The study focused on patients with metastatic castration-resistant prostate cancer (mCRPC),a particularly aggressive form of the disease affecting approximately 15% of men diagnosed with prostate cancer.
Immunotherapy, specifically checkpoint inhibitor therapy, has shown promise in treating various cancers, but its effectiveness in prostate cancer has been limited.Macrophages, a type of white blood cell, play a complex role in cancer progression. While capable of initiating anti-tumor immune responses, they can also be manipulated by tumors to suppress the immune system and promote repair, effectively shielding the cancer from attack.
“Our findings suggest that in a subset of prostate cancer patients, macrophages are actively working *against* the immune system, creating a protective barrier for the tumor,” explained Dr. Patnaik, who is also the deputy section chief for translational research in hematology and oncology at the University of Chicago Medicine. “By understanding how these macrophages are recruited and activated, we can develop strategies to reprogram them to fight cancer instead.”
The research team is now focused on developing novel drug strategies to “flip the switch” on these macrophages, converting them from tumor promoters to tumor destroyers. This approach aims to enhance the efficacy of existing immunotherapies and potentially offer a new treatment option for patients with mCRPC.
Dr. Patnaik’s personal connection to the disease – having lost an uncle to advanced prostate cancer – fuels his dedication to this research.The University of Chicago’s Biological Sciences Division has highlighted this work in its recent Medicine on the Midway magazine, underscoring the translational impact of the research from the laboratory to clinical trials.
The study involved analysis of tumor samples from 45 patients undergoing immunotherapy at the University of Chicago Medical Center. Researchers utilized single-cell RNA sequencing and spatial transcriptomics to identify the specific molecular signatures of the PD-1 expressing macrophages. Further research is planned to validate these findings in larger patient cohorts and to test the efficacy of macrophage-reprogramming strategies in preclinical models.
