Biology subjects

Crescence, L.

Publications and source records attributed to Crescence, L..

3 recordsLinked to original sources

bioRxiv2024

Consequences of platelet-educated cancer cells on the expression of inflammatory and metastatic glycoproteins.

Cancer-associated thrombosis, a major cause of mortality in cancer patients, exhibits a 4 to 7 times higher incidence compared to the general population. Platelet activation by tumor cells contributes to this pro-thrombotic state. Cancer cell-educated platelets have also been described to be implicated in promoting metastasis. Intriguingly, our team, among others, unveils a reverse process, wherein platelets educate cancer cells by transferring lipids, RNAs, and proteins. Here, focusing on colorectal and pancreatic cancers, our study investigates genes and proteins mediating platelet education of cancer cells. We demonstrated, for the first time, that platelets can educate cancer cells by inducing changes in the transcription of genes related to glycosylation, inflammation, and metastasis in cancer cells themselves. These results indicate a direct impact of platelets on cancer cell phenotype. This novel insight suggests potential therapeutic avenues for cancer treatment, disrupting platelet-mediated alterations and influencing the course of cancer progression.

cancer biology↗

bioRxiv2024

ADP-dependent platelet activation is required for thrombus formation during a long-distance flight

The association between venous thromboembolism (VTE) and air travel is well documented. Prolonged exposure to reduced atmospheric pressure and low oxygen levels during flights triggers coagulation disorders, representing the primary risk factor for Deep Vein Thrombosis (DVT), surpassing immobility. In our study, we investigated how long-distance flight conditions affect VTE development in mice exposed to 6h of hypobaric hypoxia or normobaric normoxia after inferior vena cava (IVC) ligation. We observed a pro-thrombotic profile under flight-simulated conditions, characterized by larger thrombi with higher neutrophil and fibrin densities. However, no difference was observed in neutrophil extracellular traps (NETs) or fibrin-positive neutrophils in thrombi between groups, indicating that neutrophils/NETs may not be involved in DVT development during flight. Considering the elevated ADP levels observed at high altitudes, we further assessed thrombus formation in wild-type and P2RY12-deficient mice. Remarkably, thrombus formation was no longer affected by aircraft conditions in P2RY12-deficient or wild type mice treated with clopidogrel. We conclude that ADP-induced platelet activation is involved in the development of DVT during flight, suggesting that the use of P2RY12 inhibitors may be of interest to prevent DVT in susceptible patients.

pathology↗

bioRxiv2023

Targeting BTN2A1 enhances Vγ9Vδ2 T cell effector functions and triggers tumor cells pyroptosis

V{gamma}9V{delta}2 T cells are potent but elusive cytotoxic effectors. Means to stimulate their function could lead to powerful new cancer immunotherapies. BTN2A1, a surface protein has recently been shown to bind the V{gamma}9 chain of the {gamma}{delta} TCR but its precise role in modulating V{gamma}9V{delta}2 T cells functions remains unknown. Here we show that 107G3B5, a monoclonal anti-BTN2A1 agonist antibody, significantly enhances V{gamma}9V{delta}2 T cell functions against hematological or solid cell lines and against primary cells from adult acute lymphoblastic leukemia patients. New computer vision strategies applied to holotomographic microscopy videos show that 107G3B5 enhances the interaction between V{gamma}9V{delta}2 T cells and target cells in a quantitative and qualitative manner. In addition, we provide evidence that V{gamma}9V{delta}2 T cells activated by 107G3B5 induce caspase 3/7 activation in tumor cells, thereby triggering their death by pyroptosis. We thus demonstrate that targeting BTN2A1 with 107G3B5 enhances the V{gamma}9V{delta}2 T cell antitumor response by triggering the pyroptosis-induced immunogenic cell death.

cancer biology↗