Circulating Tumour Cell Numbers Correlate with Platelet Count and Circulating Lymphocyte Subsets in Men with Advanced Prostate Cancer: Data from the ExPeCT Clinical Trial (CTRIAL-IE 15-21)

Brian Hayes*, Lauren Brady, Gráinne Sheill, Anne-Marie Baird, Emer Guinan, Bryan Stanfill, Jean Dunne, Dean Holden, Tatjana Vlajnic, Orla Casey, Verena Murphy, John Greene, Emma H. Allott, Juliette Hussey, Fidelma Cahill, Mieke Van Hemelrijck, Nicola Peat, Lorelei A. Mucci, Moya Cunningham, Liam GroganThomas Lynch, Rustom P. Manecksha, John McCaffrey, Dearbhaile M. O’Donnell, Orla Sheils, John J. O’Leary, Sarah Rudman, Ray McDermott, Stephen Finn

*Corresponding author for this work

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Abstract

Interactions between circulating tumour cells (CTCs) and platelets are thought to inhibit natural killer(NK)-cell-induced lysis. We attempted to correlate CTC numbers in men with advanced prostate cancer with platelet counts and circulating lymphocyte numbers. Sixty-one ExPeCT trial participants, divided into overweight/obese and normal weight groups on the basis of a BMI ≥ 25 or 25, were randomized to participate or not in a six-month exercise programme. Blood samples at randomization, and at three and six months, were subjected to ScreenCell filtration, circulating platelet counts were obtained, and flow cytometry was performed on a subset of samples (n = 29). CTC count positively correlated with absolute total lymphocyte count (r2 = 0.1709, p = 0.0258) and NK-cell count (r2 = 0.49, p 0.0001). There was also a positive correlation between platelet count and CTC count (r2 = 0.094, p = 0.0001). Correlation was also demonstrated within the overweight/obese group (n = 123, p 0.0001), the non-exercise group (n = 79, p = 0.001) and blood draw samples lacking platelet cloaking (n = 128, p 0.0001). By flow cytometry, blood samples from the exercise group (n = 15) had a higher proportion of CD3+ T-lymphocytes (p = 0.0003) and lower proportions of B-lymphocytes (p = 0.0264) and NK-cells (p = 0.015) than the non-exercise group (n = 14). These findings suggest that CTCs engage in complex interactions with the coagulation cascade and innate immune system during intravascular transit, and they present an attractive target for directed therapy at a vulnerable stage in metastasis.
Original languageEnglish
Article number4690
JournalCancers
Volume13
Issue number18
DOIs
Publication statusPublished - 18 Sep 2021

Keywords

  • Prostate cancer
  • circulating tumour cells
  • exercise
  • flow cytometry
  • platelets
  • inflammation
  • obesity
  • coagulation

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