Abstract Number: PB0752
Meeting: ISTH 2022 Congress
Theme: Hemostatic Systems in Cancer, Inflammation and Immunity » Platelets and Cancer
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.
Image
Circulating tumour cells [CTCs] isolated from metastatic breast [A,B] and ovarian [C] cancer patients.
To cite this abstract in AMA style:
Ward M, Kane L, Lochrin S, Ovaere C, O’Gorman C, O'Connor R, Kelly T, Mohamed B, Bates M, Carter M, Kennedy J, Tierney A, Beirne J, Kamran W, Abu Saadeh F, Cadoo K, Norris L, Martin C, O'Toole S, O'Leary J. Platelet and immune cell cloaking of circulating tumour cells [CTCs] in breast and ovarian cancer [abstract]. https://abstracts.isth.org/abstract/platelet-and-immune-cell-cloaking-of-circulating-tumour-cells-ctcs-in-breast-and-ovarian-cancer/. Accessed October 1, 2023.« Back to ISTH 2022 Congress
ISTH Congress Abstracts - https://abstracts.isth.org/abstract/platelet-and-immune-cell-cloaking-of-circulating-tumour-cells-ctcs-in-breast-and-ovarian-cancer/