PB0752 - Platelet and immune cell cloaking of circulating tumour cells [CTCs] in breast and ovarian cancer

Monday, July 11, 2022

6:30 PM – 7:30 PM

Location: Exhibition

Presentation Format: In-Person

Co-Author(s)

MW

Mark P. Ward

Research Fellow
Department of Histopathology, Trinity College Dublin, Trinity St James’s Cancer Institute, St James’s Hospital, Ireland
Dublin, Dublin, Ireland
LK

Laura E. Kane

PhD student
Trinity College Dublin
Dublin, Dublin, Ireland
SL

Sarah E. Lochrin

Medical Doctor
The Haematology, Oncology and Palliative Care (HOPe) Directorate, St James’s Hospital, Dublin 8, Ireland.
Dublin, Dublin, Ireland
CO

Celine Ovaere

Medical Doctor
Division of Gynaecological Oncology, St James’s Hospital, Dublin 8, Ireland.
Dublin, Dublin, Ireland
CO

Catherine O’Gorman

Medical Doctor
Division of Gynaecological Oncology, St James’s Hospital, Dublin 8, Ireland.
Dublin, Dublin, Ireland
RO

Roisin O'Connor

Medical Doctor
Department of Histopathology, Trinity College Dublin, Ireland.
Dublin, Dublin, Ireland
TK

Tanya E. Kelly

Research Fellow
Department of Histopathology, Trinity College Dublin, Ireland.
Dublin, Dublin, Ireland
BM

Bashir M. Mohamed

Research Fellow
Department of Histopathology, Trinity College Dublin, Ireland.
Dublin, Dublin, Ireland
MB

Mark Bates

Research Fellow
Department of Histopathology, Trinity College Dublin, Ireland.
Dublin, Dublin, Ireland
MC

Marguerite Carter

Medical Doctor
Department of Histopathology, Trinity College Dublin, Ireland.
Dublin, Dublin, Ireland
JK

John Kennedy

Consultant Medical Oncologist
The Haematology, Oncology and Palliative Care (HOPe) Directorate, St James’s Hospital, Dublin 8, Ireland.
Dublin, Dublin, Ireland
AT

Antonia Tierney

Oncology ANP
The Haematology, Oncology and Palliative Care (HOPe) Directorate, St James’s Hospital, Dublin 8, Ireland.
Dublin, Dublin, Ireland
JB

James Beirne

Consultant Gynae-oncologist
St James's Hospital
Dublin, Dublin, Ireland
WK

Waseem Kamran

Consultant Gynae-oncologist
Division of Gynaecological Oncology, St James’s Hospital, Dublin 8, Ireland.
Dublin, Dublin, Ireland
FA

Feras Abu Saadeh

Consultant Gynae-oncologist
Dept of Gynae-Oncology, Trinity St. James's Cancer Institute, Dublin 8, Ireland
Dublin, Dublin, Ireland
KC

Karen Cadoo

Consultant Medical Oncologist
Trinity St James’s Cancer Institute, St James’s Hospital, The Haematology, Oncology and Palliative Care (HOPe) Directorate, St James’s Hospital, Dublin 8, Ireland.
Dublin, Dublin, Ireland

Presenting Author(s)

Lucy A. Norris, PhD

Senior Scientist
Trinity St. James's Institute,
Dublin 8, Dublin, Ireland

Co-Author(s)

CM

Cara M. Martin

Assistant Professor
Department of Histopathology, Trinity College Dublin
Dublin, Dublin, Ireland
SO

Sharon A. O'Toole

Senior Research Fellow
Dept of Histopathology & Dept of Obstetrics and Gynaecology, Trinity St. James's Cancer Institute, St. James's Hospital, Dublin 8
Dublin, Dublin, Ireland
JO

John J. O'Leary

Professor
Dept of Histopathology, Trinity St. James Cancer Institute, St. James's Hospital, Dublin 8
Dublin, Dublin, Ireland

Background: Circulating tumour cells [CTCs] are rare, silent precursors of metastatic disease that survive in the blood circulation and metastasise to distal sites. CTCs are highly heterogeneous and often undergo EMT. Platelets and immune cells can ‘cloak’ cancer cells, aiding their survival in circulation. However, the clinical significance of platelet and immune cloaked CTCs remains unclear.

Aims: Assess the influence of platelets/neutrophils in the characterisation of CTCs from metastatic breast [MBC] and ovarian [OC] cancer patients

Methods: Platelets and neutrophils were isolated from healthy donors and co-cultured with cell lines for 24h. Markers of EMT and immune evasion were assessed by Taq-Man PCR and flow cytometry. 7.5ml peripheral blood specimens were collected prospectively from patients for CTC isolation using Parsortix; MBC [n=20] and OC [n=23] , with a subset of patients [n=10] analysed by CellSearch. Isolated CTCs were enumerated using a cancer specific CTC-ID by IF microscopy.

Results: Platelets and neutrophils altered EpCAM, TWIST1, PAI-1 and PD-L1 gene expression in OC and MBC cell lines. Platelets altered PLEK2 and CCL2 expression in MBC cells. 85% of MBC patients had >1 CTC [1-220 cells/7.5ml] while 62% of OC patients had >1 CTC [1–19 cells/7.5 ml] in blood samples. MBC CTCs clusters had immune cell cluster infiltrates, while 43% of OC CTCs were CD42b+. Follow up of CTC immunophenotyping with treatment response and survival is ongoing.

Conclusion(s): Platelet and neutrophils can alter the expression of markers of CTC detection in vitro and promote immune evasion through the up-regulation of PD-L1 and induction of EMT. CTCs isolated from patients were found to be cloaked with platelets, while CTC clusters were found to be associated with immune cells. Platelet and immune cell cloaked CTCs may be a predictive biomarker of aggressive disease in patients and aid in identifying patients with poor prognosis which may benefit from more aggressive treatment.