Myeloid-derived suppressor cells (MDSCs) in metastatic castration-resistant prostate cancer (CRPC) patients (PTS)

Date

09 Oct 2016

Session

Poster display

Presenters

Niven Mehra

Citation

Annals of Oncology (2016) 27 (6): 243-265. 10.1093/annonc/mdw372

Authors

N. Mehra1, G. Seed1, M. Lambros1, A. Sharp1, M. Sousa Fontes1, M. Crespo1, S. Sumanasuriya1, W. Yuan1, G. Boysen1, R. Riisnaes1, A. Calcinotto2, S. Carreira1, J. Goodall1, Z. Zafeiriou1, D. Bianchini1, A. Morilla3, R. Morilla3, A. Alimonti2, J.S. de Bono1

Author affiliations

  • 1 Cancer Studies, the Institute of Cancer Research (ICR), Sm2 5PT - London/GB
  • 2 Institute Of Oncology Research (ior), Oncology Institute of Southern Switzerland (IOSI), CH-6500 - Bellinzona/CH
  • 3 Centre For Molecular Pathology, Institute of Cancer Research ICR, SM2 5NG - London/GB
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Background

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.

Methods

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.

Results

Overall, 65 baseline samples were analysed from 46 PTS with 4 of 5 MDSC subsets significantly increased in CRPC samples compared to HV (Table).

Subset Phenotype CRPC (%) CRPC (N) HV (%) HV (N) P
MDSC3 CD14neg CD15neg HLA-DRlow CD33pos 0.86 65 2.17 13 0.034
MDSC9 CD14neg CD15neg CD33pos 5.76 65 5.16 13 0.373
MDSC8 CD15pos CD33pos 1.99 65 0.40 14

Conclusions

MDSC subsets are increased in CRPC, with specifically granulocytic MDSC populations associating with molecular aberrations and treatment resistance.

Clinical trial identification

Legal entity responsible for the study

Institute for Cancer Research, Johann de Bono

Funding

N/A

Disclosure

All authors have declared no conflicts of interest.

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