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 Grogan; Thomas Lynch; Rustom P. Manecksha; John McCaffrey; Dearbhaile M. O’Donnell; Orla Sheils; John J. O’leary; Sarah Rudman; Ray McDermott; Stephen Finn

doi:10.3390/cancers13184690

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

Comprehensive Cancer Centre

Research output: Contribution to journal › Article › peer-review

13 Citations (Scopus)

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-lym-phocytes (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 language	English
Article number	4690
Journal	Cancers
Volume	13
Issue number	18
Early online date	18 Sept 2021
DOIs	https://doi.org/10.3390/cancers13184690
Publication status	Published - Sept 2021

Keywords

Circulating tumour cells
Coagulation
Exercise
Flow cytometry
Inflamma-tion
Obesity
Platelets
Prostate cancer

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.3390/cancers13184690

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Hayes, B., Brady, L., Sheill, G., Baird, A. M., Guinan, E., Stanfill, B., Dunne, J., Holden, D., Vlajnic, T., Casey, O., Murphy, V., Greene, J., Allott, E. H., Hussey, J., Cahill, F., Van Hemelrijck, M., Peat, N., Mucci, L. A., Cunningham, M., ... Finn, S. (2021). 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). Cancers, 13(18), Article 4690. https://doi.org/10.3390/cancers13184690

@article{f9db2c5e95964e1b8bd12b77ddf95a66,

title = "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)",

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-lym-phocytes (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.",

keywords = "Circulating tumour cells, Coagulation, Exercise, Flow cytometry, Inflamma-tion, Obesity, Platelets, Prostate cancer",

author = "Brian Hayes and Lauren Brady and Gr{\'a}inne Sheill and Baird, {Anne Marie} and Emer Guinan and Bryan Stanfill and Jean Dunne and Dean Holden and Tatjana Vlajnic and Orla Casey and Verena Murphy and John Greene and Allott, {Emma H.} and Juliette Hussey and Fidelma Cahill and {Van Hemelrijck}, Mieke and Nicola Peat and Mucci, {Lorelei A.} and Moya Cunningham and Liam Grogan and Thomas Lynch and Manecksha, {Rustom P.} and John McCaffrey and O{\textquoteright}Donnell, {Dearbhaile M.} and Orla Sheils and O{\textquoteright}leary, {John J.} and Sarah Rudman and Ray McDermott and Stephen Finn",

note = "Funding Information: Conflicts of Interest: The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results. A.-M.B. declares board membership of LuCE which has received support from Abbvie, Amgen, B.M.S., B.I., Lilly, Merck, M.S.D., Novartis, Pfizer, Roche and Takeda, advisory boards for BMS, Takeda and Pfizer and personal fees and non-financial support from Roche, personal fees and nonfinancial support from M.S.D., outside the submitted work. B.S. reports funding from Trinity College Dublin throughout the conduct of this study. E.G. and M.V.H. report membership of the editorial board of BMC Cancer. D.M.O. reports non-financial support from Astra Zeneca, outside the current study. R.M. reports personal fees from Clovis, grants and personal fees from Pfizer, grants from Amgen, personal fees and other from Bristol Myers Squibb, other from Merck, Bayer and Janssen and grants from Celgene outside the submitted work. J.J.O. reports professional fees from Roche and Hologic outside the submitted work. S.F. reports personal fees and non-financial support from Pfizer, grants, personal fees and non-financial support from M.S.D., personal fees and nonfinancial support from Roche, grants, personal fees and non-financial support from Astellas, outside the submitted work. Funding Information: Funding: This research was sponsored by Cancer Trials Ireland (CTRIAL-IE 15-21) and funded by the World Cancer Research Fund (grant number 2012/1003). Publisher Copyright: {\textcopyright} 2021 by the author. Licensee MDPI, Basel, Switzerland. Copyright: Copyright 2021 Elsevier B.V., All rights reserved.",

year = "2021",

month = sep,

doi = "10.3390/cancers13184690",

language = "English",

volume = "13",

journal = "Cancers",

issn = "2072-6694",

publisher = "Multidisciplinary Digital Publishing Institute (MDPI)",

number = "18",

}

Hayes, B, Brady, L, Sheill, G, Baird, AM, Guinan, E, Stanfill, B, Dunne, J, Holden, D, Vlajnic, T, Casey, O, Murphy, V, Greene, J, Allott, EH, Hussey, J, Cahill, F, Van Hemelrijck, M, Peat, N, Mucci, LA, Cunningham, M, Grogan, L, Lynch, T, Manecksha, RP, McCaffrey, J, O’Donnell, DM, Sheils, O, O’leary, JJ, Rudman, S, McDermott, R & Finn, S 2021, '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)', Cancers, vol. 13, no. 18, 4690. https://doi.org/10.3390/cancers13184690

TY - JOUR

T1 - Circulating tumour cell numbers correlate with platelet count and circulating lymphocyte subsets in men with advanced prostate cancer

T2 - 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 - Van Hemelrijck, Mieke

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

N1 - Funding Information: Conflicts of Interest: The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results. A.-M.B. declares board membership of LuCE which has received support from Abbvie, Amgen, B.M.S., B.I., Lilly, Merck, M.S.D., Novartis, Pfizer, Roche and Takeda, advisory boards for BMS, Takeda and Pfizer and personal fees and non-financial support from Roche, personal fees and nonfinancial support from M.S.D., outside the submitted work. B.S. reports funding from Trinity College Dublin throughout the conduct of this study. E.G. and M.V.H. report membership of the editorial board of BMC Cancer. D.M.O. reports non-financial support from Astra Zeneca, outside the current study. R.M. reports personal fees from Clovis, grants and personal fees from Pfizer, grants from Amgen, personal fees and other from Bristol Myers Squibb, other from Merck, Bayer and Janssen and grants from Celgene outside the submitted work. J.J.O. reports professional fees from Roche and Hologic outside the submitted work. S.F. reports personal fees and non-financial support from Pfizer, grants, personal fees and non-financial support from M.S.D., personal fees and nonfinancial support from Roche, grants, personal fees and non-financial support from Astellas, outside the submitted work. Funding Information: Funding: This research was sponsored by Cancer Trials Ireland (CTRIAL-IE 15-21) and funded by the World Cancer Research Fund (grant number 2012/1003). Publisher Copyright: © 2021 by the author. Licensee MDPI, Basel, Switzerland. Copyright: Copyright 2021 Elsevier B.V., All rights reserved.

PY - 2021/9

Y1 - 2021/9

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-lym-phocytes (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-lym-phocytes (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 - Circulating tumour cells

KW - Coagulation

KW - Exercise

KW - Flow cytometry

KW - Inflamma-tion

KW - Obesity

KW - Platelets

KW - Prostate cancer

UR - http://www.scopus.com/inward/record.url?scp=85115058190&partnerID=8YFLogxK

U2 - 10.3390/cancers13184690

DO - 10.3390/cancers13184690

M3 - Article

AN - SCOPUS:85115058190

SN - 2072-6694

VL - 13

JO - Cancers

JF - Cancers

IS - 18

M1 - 4690

ER -

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)

Abstract

Keywords

UN SDGs

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