TY - JOUR
T1 - 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)
AU - Hayes, Brian
AU - Brady, Lauren
AU - Sheill, Gráinne
AU - Baird, Anne-Marie
AU - Guinan, Emer
AU - Stanfill, Bryan
AU - Dunne, Jean
AU - Holden, Dean
AU - Vlajnic, Tatjana
AU - Casey, Orla
AU - Murphy, Verena
AU - Greene, John
AU - Allott, Emma H.
AU - Hussey, Juliette
AU - Cahill, Fidelma
AU - Hemelrijck, Mieke Van
AU - Peat, Nicola
AU - Mucci, Lorelei A.
AU - Cunningham, Moya
AU - Grogan, Liam
AU - Lynch, Thomas
AU - Manecksha, Rustom P.
AU - McCaffrey, John
AU - O’Donnell, Dearbhaile M.
AU - Sheils, Orla
AU - O’Leary, John J.
AU - Rudman, Sarah
AU - McDermott, Ray
AU - Finn, Stephen
PY - 2021/9/18
Y1 - 2021/9/18
N2 - 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.
AB - 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.
KW - Prostate cancer
KW - circulating tumour cells
KW - exercise
KW - flow cytometry
KW - platelets
KW - inflammation
KW - obesity
KW - coagulation
U2 - 10.3390/cancers13184690
DO - 10.3390/cancers13184690
M3 - Article
SN - 2072-6694
VL - 13
JO - Cancers
JF - Cancers
IS - 18
M1 - 4690
ER -