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)

Journal Article · 18 September 2021 · Cancers (Basel)

DOI: https://doi.org/10.3390/cancers13184690 · OSTI ID:2471584

Hayes, Brian  ^[1]; Brady, Lauren ^[2]; Sheill, Gráinne ^[2]; Baird, Anne-Marie ^[2]; Guinan, Emer ^[2]; Stanfill, Bryan ^[3]; Dunne, Jean ^[4]; Holden, Dean ^[4]; Vlajnic, Tatjana ^[5]; Casey, Orla ^[6]; Murphy, Verena ^[6]; Greene, John ^[2]; Allott, Emma H. ^[7]; Hussey, Juliette ^[2]; Cahill, Fidelma ^[8]; Van Hemelrijck, Mieke ^[8]; Peat, Nicola ^[9]; Mucci, Lorelei A. ^[10]; Cunningham, Moya ^[11]; Grogan, Liam ^[12] ; Lynch, Thomas ^[4]; Manecksha, Rustom P. ^[13]; McCaffrey, John ^[14]; O’Donnell, Dearbhaile M. ^[4]; Sheils, Orla ^[2]; O’Leary, John J.  ^[15]; Rudman, Sarah ^[9]; McDermott, Ray ^[16]; Finn, Stephen  ^[17]

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1. Cork University Hospital (Ireland); University College Cork (Ireland)
2. Trinity College Dublin (Ireland)
3. Pacific Northwest National Laboratory (PNNL), Richland, WA (United States)
4. St. James’s Hospital, Dublin (Ireland)
5. University Hospital Basel (Switzerland)
6. Cancer Trials Ireland, Dublin (Ireland)
7. Trinity College Dublin (Ireland); Queen’s University, Belfast, Northern Ireland (United Kingdom)
8. King's College, London (United Kingdom)
9. Guy’s and St. Thomas’ NHS Foundation Trust, London (United Kingdom)
10. Harvard T.H. Chan School of Public Health, Boston, MA (United States)
11. St. Luke’s Hospital, Dublin (Ireland)
12. Beaumont Hospital, Dublin (Ireland)
13. St. James’s Hospital, Dublin (Ireland); Trinity College Dublin (Ireland)
14. Mater Misericordiae Hospital, Dublin (Ireland)
15. Trinity College Dublin (Ireland); St. James’s Hospital, Dublin (Ireland)
16. Department of Oncology, Tallaght University Hospital, Dublin (Ireland)
17. Trinity College Dublin (Ireland); Cancer Trials Ireland, Dublin (Ireland); St. James’s Hospital, Dublin (Ireland)

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.

• Research Organization: Pacific Northwest National Laboratory (PNNL), Richland, WA (United States)
• Sponsoring Organization: USDOE; World Cancer Research Fund (WCRF)
• Grant/Contract Number: AC05-76RL01830
• OSTI ID: 2471584
• Journal Information: Cancers (Basel), Journal Name: Cancers (Basel) Journal Issue: 18 Vol. 13; ISSN 2072-6694
• Publisher: MDPICopyright Statement
• Country of Publication: United States
• Language: English