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
3988 - Basal NK activity and early Treg function inhibition predicts Nivolumab responsiveness in metastatic renal cancer patients (REVOLUTION) trial.
Presenter: Sara Santagata
Session: Poster Display session 3
Resources:
Abstract
2142 - Low NK Cell Abundance Correlates with High Expression of PD-1 in CD8+ T Cells
Presenter: Moon Hee Lee
Session: Poster Display session 3
Resources:
Abstract
5501 - Tobacco smoking is associated with the immune suppressive microenvironment in head and neck squamous cell carcinoma (HNSCC)
Presenter: Christine Chung
Session: Poster Display session 3
Resources:
Abstract
5726 - Evaluation of Antibody-Dependent Cell Cytotoxicity (ADCC) in lung cancer cell lines treated with combined anti-EGFR and anti-PD-L1 therapy.
Presenter: Francesca Sparano
Session: Poster Display session 3
Resources:
Abstract
2534 - Radiomic Signatures for Identification of Tumors Sensitive to Nivolumab or Docetaxel in Squamous Non-Small Cell Lung Cancer (sqNSCLC)
Presenter: Laurent Dercle
Session: Poster Display session 3
Resources:
Abstract
3366 - Analysis of gut microbiota in advanced non-small cell lung cancer (NSCLC) patients treated with immune-checkpoints blockers
Presenter: FEIYU ZHANG
Session: Poster Display session 3
Resources:
Abstract
2089 - Pathogenesis of Myocarditis Following Treatment with Immune Checkpoint Inhibitors in a Cynomolgus Monkey Model
Presenter: Changhua Ji
Session: Poster Display session 3
Resources:
Abstract
4463 - Effects of dietary restriction in cancer patients receiving irinotecan
Presenter: Ruben Van Eerden
Session: Poster Display session 3
Resources:
Abstract
4841 - Investigating the Link between Burn Injury and Tumorigenesis
Presenter: Lucy Barrett
Session: Poster Display session 3
Resources:
Abstract
4619 - Prognostic value of the neutrophil-lymphocyte, platelet-lymphocyte and monocyte-lymphocyte ratio in male breast cancer patients
Presenter: Joanna Huszno
Session: Poster Display session 3
Resources:
Abstract