ASCO GU 2018: Expression of Immune Checkpoints on Circulating Tumor Cells in Men with Metastatic Prostate Cancer
Patients were enrolled prospectively at the Duke Cancer Center in three cohorts: A) mCRPC starting the novel androgen receptor inhibitors abiraterone acetate (AA) or enza with or without sipuleucel-T, B) mCRPC with disease progression after AA or enza, and C) metastatic castration sensitive PC. The Cellsearch platform was used to capture EpCAM- and CK-expressing CTCs and analyzed for PD-L1, PD-L2, B7-H3, and CTLA-4 expression at baseline, 12 weeks, and at further disease progression.
Through August 2017, we enrolled 4 subjects in cohort A, 7 in cohort B, and 3 in cohort C. CTCs were detectable in every cohort. At baseline, B7-H3 was the most prevalent IC on a per-patient basis (mean 96% in cohort A, and 100% in cohort B, and 88% in cohort C). PD-L1 was detected less frequently (cohort A mean 8%, cohort B mean 42%, and cohort C mean 67%), with evidence of heterogeneity of CTC PD-L1 expression between and within patients. PD-L1 was expressed on 8% of CTCs in cohort C and cohort A, as compared to 28% of CTCs in cohort B, while CTLA-4 expression was not identified in cohort C, 3% of cohort A, and 15% of cohort B. B7H3 was expressed on 68% of cohort C, 91% of cohort A, and 98% of cohort B. PD-L2 was expressed on 0-7% of CTCs overall.
Patients with mPC can have detectable and heterogeneous ICs on CTCs, particularly PD-L1 and B7-H3, and these characteristics can be monitored over time. B7-H3 was the most prevalent IC on CTCs, regardless of disease state. Our preliminary data suggest that men with mCRPC post-enza/AA have higher levels of PD-L1 and CTLA-4 expression on their CTCs as compared with men with mHSPC and mCRPC prior to enza/AA. Patient enrollment and analysis are ongoing.
Presented by: Tian Zhang, MD
Co Authors: Rebecca Garland Austin, Sally E Park, Daniella Runyambo, Rengasamy Boominathan, Chandra Rao, Elizabeth Bronson, Monika Anand, Patrick Healy, Daniel J. George, Megan Ann McNamara, Andrew J. Armstrong; Duke University Medical Center, Durham, NC; Emory University School of Medicine, Atlanta, GA; Albert Einstein College of Medicine, New York, NY; Duke Cancer Institute, Duke University, Durham, NC; Veridex LLC, Huntingdon Valley, PA; Duke University, Durham, NC; Duke University Medical Center, Mornsville, NC
Presented at the 2018 American Society of Clinical Oncology Genitourinary (ASCO GU) Cancers Symposium, February 8-10, 2018 - San Francisco, CA