Abstract 1122
Background
Platelet activation by tumour cells contributes to critical steps in the formation of metastases. Mechanisms include protection of tumour cells from immune destruction, interaction of platelet receptors with tumour ligands to facilitate adhesion, and enrichment of the tumour microenvironment to promote extravasation and proliferation. This study investigated the differences in platelet activation markers in cancer patients compared to healthy donors, and the effect of the addition of in vitro antiplatelet agents.
Methods
Blood was collected from consented healthy volunteers and patients with metastatic cancer. Platelet rich plasma was prepared. Light transmission aggregometry measured spontaneous aggregation of platelet samples, without the addition of exogenous agonists. Flow cytometry measured the platelet activation markers P-selectin and fibrinogen binding on unstimulated, untreated platelets, and on unstimulated platelets incubated with aspirin, Ticagrelor and dual antiplatelet therapy.
Results
62 cancer patients and 17 healthy donors provided blood samples. There was increased spontaneous aggregation of platelets from cancer patients compared to healthy platelets (9±1.1% vs 4±0.9% p = 0.02). Platelets from cancer patients had increased basal levels of P-selectin expression compared to healthy platelets (17.2±2.7% vs 8.4±0.3%) and incubation of platelets with antiplatelets had no effect. There was no difference in the basal level of fibrinogen binding between populations, however incubation with dual antiplatelet therapy reduced baseline fibrinogen binding in platelets from cancer patients (3.1±0.7% vs 10.8±3.7%).
Conclusions
Platelets from cancer patients are hyperactive and easily form aggregates compared to healthy platelets. Platelets from cancer patients have higher levels of the activation marker P-selectin. Aggregation requires fibrinogen binding and incubation with dual antiplatelet therapy reduces this binding in platelets from cancer patients. The interaction between tumour cells and platelets could be a potential biomarker of disease, and this is reduced by antiplatelet drugs. Further studies determining the effect of in vivo antiplatelet therapy on platelets in cancer patients are being undertaken.
Clinical trial identification
EudraCT: 2014‐004049‐29; Start date: 10‐03‐2015.
Editorial acknowledgement
Legal entity responsible for the study
University of Leicester.
Funding
AstraZeneca.
Disclosure
A. Thomas: Advisory / Consultancy: Bristol-Myers Squibb; Advisory / Consultancy: Pierre Fabre; Advisory / Consultancy, Speaker Bureau / Expert testimony: Amgen. A. Goodall: Research grant / Funding (institution): Hoffmann La Roche; Research grant / Funding (institution): AstraZeneca. D. Adlam: Research grant / Funding (institution): Abbott Vascular Inc; Research grant / Funding (institution): AstraZeneca. All other authors have declared no conflicts of interest.
Resources from the same session
1885 - Factors associated with disease progression in patients treated with trametinib in combination with dabrafenib for unresectable advanced BRAFV600-mutant melanoma: an open label, non randomized study
Presenter: Philippe Saiag
Session: Poster Display session 3
Resources:
Abstract
5259 - Integrative RNAseq and Target panel sequencing reveals common and distinct innate and adaptive resistance mechanisms to BRAF inhibitors
Presenter: Phil Cheng
Session: Poster Display session 3
Resources:
Abstract
5619 - Effective treatment with T-VEC monotherapy in Stage IIIB/C-IVM1a Melanoma of the Head & Neck Region
Presenter: Viola Franke
Session: Poster Display session 3
Resources:
Abstract
5666 - Re-introduction of T-VEC Monotherapy in Recurrent Stage IIIB/C-IVM1a melanoma is effective
Presenter: Viola Franke
Session: Poster Display session 3
Resources:
Abstract
4117 - Efficacy of talimogene laherparepvec (T-VEC) in melanoma patients (pts) with locoregional (LR) recurrence, including in-transit metastases (ITM): subgroup analysis of the phase 3 OPTiM study
Presenter: Mark Middleton
Session: Poster Display session 3
Resources:
Abstract
5303 - Real Life Use of Talimogene Laherparepvec in Melanoma in Centers in Austria and Switzeland
Presenter: Christoph Hoeller
Session: Poster Display session 3
Resources:
Abstract
4130 - Outcomes of advanced melanoma patients who discontinued pembrolizumab (pembro) after complete response (CR) in the French early access program (EAP)
Presenter: Philippe Saiag
Session: Poster Display session 3
Resources:
Abstract
2050 - Outcome of patients with elevated LDH treated with first-line targeted therapy (TT) or PD-1 based immune checkpoint inhibitors (ICI)
Presenter: Sarah Knispel
Session: Poster Display session 3
Resources:
Abstract
1618 - Comparative-Effectiveness of Pembrolizumab vs. Nivolumab for Patients with Metastatic Melanoma
Presenter: Justin Moser
Session: Poster Display session 3
Resources:
Abstract
3556 - Long-term efficacy of combination nivolumab and ipilimumab for first-line treatment of advanced melanoma: a network meta-analysis
Presenter: Peter Mohr
Session: Poster Display session 3
Resources:
Abstract