**3.2.2 Myeloid cells**

198 Prostate Cancer – Diagnostic and Therapeutic Advances

inflammatory responses, respectively. CD4+, CD8+ and regulatory T cells are all present in PCa tumour tissue, with CD8+ T cells being predominant, unlike in the peripheral blood where CD4+ T cell frequencies are higher (Bronte et al., 2005). The majority of tumourinfiltrating CD8+ T cells are memory or terminally differentiated cells but their ability to upregulate activation markers is impaired (Bronte et al., 2005; Drake, 2010). In radical prostatectomy specimens of PCa, IFN-γ and perforin expression is lower than in T cells in healthy prostate tissue (Ebelt et al., 2008). Lymphocytes can mainly be observed in clusters

Fig. 1. (A-C) PCa prostatectomy sections stained with haematoxylin and eosin shown at increasing magnifications; (C) a region with glandular () and stromal areas (). (D) peritumoural CD8+ T lymphocyte cluster, identified by fluorescence microscopy. (E) CD4+

T cells with regulatory function (CD4+CD25+Foxp3+) are present at higher frequencies in PCa than in healthy tissue. They can be found mainly in T cell clusters surrounding prostate cancer lesions or in the stroma (Ebelt et al., 2009; Miller et al., 2006; Sfanos et al., 2008). Some of these Treg cells express the glucocorticoid-induced TNF-receptor (GITR) and ICOS (a CD28-superfamily costimulatory molecule) at higher levels than in blood, indicating recent

cells are also present in this region.

in peritumoural areas while only a few infiltrate the tumour areas (Fig. 1).

CD68+ monocytes and macrophages have been observed at higher frequencies in PCa compared to benign prostate tissues in a Gleason-score and disease stage-associated manner (Lindholm et al., 2010). CD68+ monocytes and less differentiated CD11b+CD33+ myeloid cells have been shown by immunohistochemistry to be present in PCa stroma (Sorrentino et al., 2011). There is no information available as to whether these cells function as tumourassociated macrophages (TAM) or myeloid-derived suppressor cells (MDSC). Monocytic MDSC have been characterised as CD11b+, CD14+, CD15+/-, CD16-, CD33+, CD66b+, CD124+, VEGFR1- and HLA-DRlow cells (Gabrilovich & Nagaraj, 2009; Marigo et al., 2008). More work is needed to establish if immunosuppressive MDSC are present in the microenvironment in PCa. Myeloid-derived dendritic cells (DC) have also been documented in PCa tissues although at relatively low frequencies and in a minimally activated state (Troy et al., 1998).
