Abstract 2449
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 | ConclusionsMDSC subsets are increased in CRPC, with specifically granulocytic MDSC populations associating with molecular aberrations and treatment resistance. Clinical trial identificationLegal entity responsible for the studyInstitute for Cancer Research, Johann de Bono FundingN/A DisclosureAll authors have declared no conflicts of interest. Resources from the same session2354 - The clinicopathologic features and treatment of 607 hindgut neuroendocrine tumor (NET) patients at a single institutionPresenter: Seung Tae Kim Session: Poster Display Resources: Abstract 2594 - Neuroendocrine carcinomas of the colorectal origin - Polish experiencePresenter: Agnieszka Kolasińska-Ćwikła Session: Poster Display Resources: Abstract 2539 - Neuroendocrine neoplasms of the appendix including goblet cell carcinoidsPresenter: Agnieszka Kolasinska-Cwikla Session: Poster Display Resources: Abstract 1245 - Prognostic validity of AJCC staging system in neuroendocrine tumors of the appendixPresenter: Amir Mehrvarz Sarshekeh Session: Poster Display Resources: Abstract 3902 - Enhancer of zest homolog 2 (EZH2) expression in well and moderately differentiated pancreatic neuroendocrine tumor (pNET)Presenter: Riccardo Marconcini Session: Poster Display Resources: Abstract 3882 - Differential clinical and pathological characteristics of hereditary neuroendocrine pancreatic tumours (NEPT)Presenter: Gema Marín Zafra Session: Poster Display Resources: Abstract 2296 - Natural course of thyroid cancer nodules compared with benign thyroid nodulesPresenter: Kyung-Jin Yun Session: Poster Display Resources: Abstract 4083 - Reassessment of proliferative activity at disease progression in neuroendocrine neoplasmsPresenter: Noemi Cicchese Session: Poster Display Resources: Abstract 3866 - 18F-FDG-PET to predict disease progression in advanced digestive neuroendocrine neoplasmsPresenter: Maria Rinzivillo Session: Poster Display Resources: Abstract 3651 - UK phase IV, observational study to assess quality of life in patients (pts) with pancreatic neuroendocrine tumours (pNETS) receiving treatment with everolimus: The “real-world” OBLIQUE studyPresenter: John Ramage Session: Poster Display Resources: Abstract This site uses cookies. Some of these cookies are essential, while others help us improve your experience by providing insights into how the site is being used. For more detailed information on the cookies we use, please check our Privacy Policy.
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