Abstract Number: OC 58.4
Meeting: ISTH 2021 Congress
Theme: Role of Hemostatic System in Cancer, Inflammation and Immunity » Platelets and Cancer
Background: Platelets help facilitate hematogenous metastasis in part by promoting cancer cell immunoevasion, although our understanding of platelet function in modulating the adaptive immune system in cancer is limited. A major negative regulator of the adaptive response is the immune checkpoint protein Programmed Death Ligand 1 (PD-L1).
Aims: As platelets secrete factors that may increase PD-L1 expression, we investigated whether they up-regulate cancer cell PD-L1, thus promoting immunoevasion, and whether common anti-platelet drugs inhibit this process.
Methods: Platelets were isolated from human volunteers. A549 lung, PD-L1 null A549, and 786-O renal cancer cells were incubated with and without platelets, and cancer cell PD-L1 expression was measured by qPCR and flow cytometry. Additionally, platelet-cancer cell incubations were performed in the presence of common anti-platelet drugs, and with growth factor neutralizing antibodies. Following incubation with platelets, A549 cells were co-cultured with Jurkat cells and interleukin-2 (IL-2) levels were measured by flow cytometry as a marker of T-cell activation.
Results: Platelets increased PD-L1 mRNA and surface protein expression by A549 and 786-0 cells. Combined neutralization of VEGF and PDGF prevented the platelet-induced up-regulation of PD-L1 by A549 cells, as did the anti-platelet drug eptifibatide. A549 incubated with platelets demonstrated a reduced ability to activate Jurkat cells and this effect was reversed by eptifibatide.
Conclusions: As platelets promote immunoevasion of the adaptive immune response by increasing cancer cell PD-L1 expression and as anti-platelet drugs prevent this immunoevasive response, the investigation of anti-platelet drugs as adjuvant therapy to immune checkpoint inhibitors may be warranted in the treatment of cancer
To cite this abstract in AMA style:
Asgari A, Lesyk G, Poitras E, Govindasamy N, Terry K, To R, Back V, Rudzinski J, Lewis J, Jurasz P. Platelets Stimulate Programmed Death-ligand 1 Expression by Cancer Cells: Inhibition by Anti-platelet Drugs [abstract]. Res Pract Thromb Haemost. 2021; 5 (Suppl 2). https://abstracts.isth.org/abstract/platelets-stimulate-programmed-death-ligand-1-expression-by-cancer-cells-inhibition-by-anti-platelet-drugs/. Accessed March 22, 2024.« Back to ISTH 2021 Congress
ISTH Congress Abstracts - https://abstracts.isth.org/abstract/platelets-stimulate-programmed-death-ligand-1-expression-by-cancer-cells-inhibition-by-anti-platelet-drugs/