The relevance of targeting MDSCs in CRPC is increasingly recognized; preclinical studies implicate MDSCs with senescence evasion, treatment resistance, loss of tumour suppressors (TSL) function or oncogene activation (OA). We investigated MDSC subsets in CRPC PTS with regard to their molecular underpinnings and associated with PSA response.
We prospectively evaluated MDSCs in 46 progressing CRPC PTS prior to new lines of therapy (n = 65), and in 14 male healthy volunteers (HV). Following blood draw MDSCs were analysed within 24 hours according to a gating strategy designed to standardize MDSC phenotyping. Here we report 5 MDSC subsets (phenotypes described in table), of which 2 are monocytic (M)/granulocytic (Gr) lineage-negative (MDSC3 and MDSC9), 2 with Gr (MDSC8 and MDSC8A) and 1 with a M phenotype (MDSC4). Subsets are expressed as % of their parental population. Data were acquired with a BD Canto II with FACS-Diva and analysed using Kaluza 1.3. We tested for the association between MDSCs subsets and copy number aberrations of 8q gain, loss (het/homdel) of PTEN and RB1 in cell-free circulating DNA by targeted amplicon-based sequencing (IonTorrent) using CNVkit V0.3.5. Differences in levels of the 5 MDSC subsets were assessed using non-parametric testing (Mann-Whitney) and associations of dichotomized MDSC subsets (at median) with PSA response were tested by Chi-square.
Overall, 65 baseline samples were analysed from 46 PTS with 4 of 5 MDSC subsets significantly increased in CRPC samples compared to HV (Table).