Abstract 1078: An immunosuppressive signature in bone marrow as a potential biomarker for recurrence of metastatic prostate cancer after prostatectomy
Authors: Sethakorn Nan , Heninger Erika , Sperger Jamie M. , Pienta Kenneth J. , Lang Joshua M. 
Published: August 2019

Background: Metastatic prostate cancer is the second leading cause of cancer-related deaths in US men. Nearly one-third of men develop recurrence after curative intent treatment. Bone metastases are common, and cause significant morbidity in addition to driving mortality rates. Early dissemination of tumor cells to the bone marrow has been hypothesized as a contributing factor to recurrence. However, the factors that promote early dissemination and survival in the bone microenvironment are not clearly elucidated. Key components of immune regulation such as cytotoxic T cells and regulatory T cells can regulate growth of cancer cell lines and in mouse models. We hypothesize that an immunosuppressive signature results in a permissive environment allowing the growth of disseminated prostate cancer cells. Therefore, the goal of our project is to evaluate mechanisms of immune evasion that promote the development of metastatic prostate cancer.

Methods: Matched blood and bone marrow aspirates were collected from patients undergoing prostatectomy. Samples from five healthy donors were collected to establish a normal baseline. Using multicolor flow cytometry, samples were subjected to multi-parameter panels designed to assess the composition and function of lymphoid and myeloid immune compartments. These panels include markers of known immune subtypes, co-stimulatory signals, and activation signals. Results were analyzed with Prism software.

Results: Preliminary results show variable T cell to B cell ratios ranging from as low as 1:1 to as high as 9:1. A high CD4 to CD8 T cell ratio was identified in 38% of samples, which corresponded with a higher occurrence of regulatory T cells. These data are consistent with an immunosuppressed bone marrow signature, which importantly was not present in the matched peripheral blood samples. Furthermore, our preliminary data demonstrates altered lymphoid and myeloid subsets in patients with prostate cancer as compared to healthy donors.

Discussion: Overall, these results support the hypothesis that an immunosuppressive signature in bone marrow may promote survival of disseminated prostate cancer cells by protecting them from immune eradication. Furthermore, this immune signature within the microenvironment may exist at the time of prostatectomy and can be correlated with clinical biomarkers to identify factors that promote dissemination and metastatic recurrence. Future work involves using descriptive statistics to correlate the immune signatures identified in this project with patient outcomes, including PSA, Gleason grade, recurrence rates and time to recurrence. Ultimately, the goal is to identify an immune signature that accurately predicts risk of developing recurrent prostate cancer, potentially serving as a biomarker for patients that would benefit from aggressive upfront adjuvant systemic therapy.

Citation Format: Nan Sethakorn, Erika Heninger, Jamie M. Sperger, Kenneth J. Pienta, Joshua M. Lang. An immunosuppressive signature in bone marrow as a potential biomarker for recurrence of metastatic prostate cancer after prostatectomy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 1078.