RESUMEN
Chronic inflammation in the benign prostate has been associated with a higher risk of developing prostate cancer. While a range of immune lineages is found in the prostate including T cells, B cells and myeloid cells, the specific subsets of immune cells with each major lineage have not been well described. In this study, we use mass cytometry (CyTOF) to comprehensively and reproducibly profile immune cells in mouse and human prostate. Using 4 myeloid markers (CD11b, CD11c, F4/80, Ly6C) in the mouse, we identified 8 phenotypically-distinct myeloid populations, demonstrating considerable heterogeneity within the immune compartment of the mouse prostate. We then profiled the prostate immune microenvironment from 9 human patients. Unlike the mouse prostate which is myeloid-dominant, the immune compartment in the benign human prostate is consistently T-lymphocyte-dominant. Using the X-shift algorithm to identify individual immune subsets based on marker expression, we found 57 phenotypically-distinct immune cell types in the human prostate. Despite similar proportions of T, B and myeloid lineage cells in the benign human prostate of all patients evaluated, we observed considerable interpatient heterogeneity in the abundance of more specific immune subsets. These findings highlight the importance of studying the immune compartment in the prostate at a granular level and will lead to future studies addressing the functional role of specific immune subsets in prostate epithelial transformation.
RESUMEN
Aging is associated with loss of tissue mass and a decline in adult stem cell function in many tissues. In contrast, aging in the prostate is associated with growth-related diseases including benign prostatic hyperplasia (BPH). Surprisingly, the effects of aging on prostate epithelial cells have not been established. Here we find that organoid-forming progenitor activity of mouse prostate basal and luminal cells is maintained with age. This is caused by an age-related expansion of progenitor-like luminal cells that share features with human prostate luminal progenitor cells. The increase in luminal progenitor cells may contribute to greater risk for growth-related disease in the aging prostate. Importantly, we demonstrate expansion of human luminal progenitor cells in BPH. In summary, we define a Trop2+ luminal progenitor subset and identify an age-related shift in the luminal compartment of the mouse and human prostate epithelium.