Immune profiling and organoids generation of a rare case of prostate cancer liver metastasis.

Introduction: Prostate cancer (PCa) is the second most frequent cancer in men and a leading cause of cancer-related mortality. Despite major advances in immunotherapy, PCa remains a poor responder. Metastatic PCa is responsible for the majority of PCa-associated mortality. Most PCa metastases are multifocal and display a strong bones tropism (91.1% of cases), but PCa metastases can also spread to the lymph nodes (8.7%), lungs (5.7%), liver (4.5%) and brain (1.8%). Liver metastases are associated with worse prognosis but due to their multifocal nature and frequent spreading to other sites, PCa metastases are rarely resected. Therefore, immunologic characterization of these lesions concomitant with generation of research tools derived from these lesions are urgently needed to understand how to intercept disease progression. Methods: A 62-year-old male who previously underwent radical prostatectomy in 2016 was diagnosed in July 2018 with a single liver metastasis (5.3 cm) by MRI. The tumor was surgically resected and tumor tissue along with peripheral blood was collected and processed for in-depth immunologic/molecular characterization and generation of tumor models. The study was done in accordance with the guidelines approved by MUHC IRB. Prior written informed consent was obtained from the subject to participate in the study (protocol: SDR-11-066). Results: The prostatic origin of the tumor mass was confirmed by positivity for PSMA and NKX3.1 expression. Patient-derived xenografts, 2D cell and organoid cultures were generated and immunophenotyping of the innate and adaptive peripheral and tumor-infiltrating immune cells subsets was performed. Genomic alterations are currently being characterized by multiplex ligation-dependent probe amplification (MLPA). Additionally, chromatin accessibility-based characterization of the gene regulatory network of tumor luminal cells (CD49-CD26+) using the assay for transposase-accessible chromatin using sequencing (ATAC-seq) together with RNA-seq is presently under way. Conclusions: Our collaborative effort will provide the much-needed research tools required to model and understand the processes leading to the rare, but lethal, progression from a localized PCa lesion to liver metastases. Combined with other ongoing research efforts, we believe this case will help us understand the molecular basis to the liver tropism of a subset of PCa metastases and ultimately provide biomarkers for early identification of patients with increased metastatic potential as well as a basis to determine the appropriate immunotherapy modality for metastatic patients. Citation Format: Aurelie Y. Le Page, Anna de Polo, K-P Guerard, A. Lazaris, S.K. Petrillo, W. Ebrahimizadeh, S. Tabaries, S. Shinde-Jadhav, A. Feldiorean, N. Boufaeid, W. Kassouf, C. Piccirillo, P.M. Siegel, A. Aprikian, A. Gregorieff, J. Lapointe, P. Metrakos, D.P. Labbe. Immune profiling and organoids generation of a rare case of prostate cancer liver metastasis [abstract]. In: Proceedings of the AACR Special Conference on Tumor Immunology and Immunotherapy; 2018 Nov 27-30; Miami Beach, FL. Philadelphia (PA): AACR; Cancer Immunol Res 2020;8(4 Suppl):Abstract nr A26.