Molecular Landscape of the Coagulome of Oral Squamous Cell Carcinoma

Simple Summary Cancer is associated with a wide spectrum of hemostatic complications that range from thrombotic events to hemorrhage. The tumor coagulomes, i.e., the essential actors that locally regulate coagulation and fibrinolysis, play a key role in these complications. They might also play a regulatory role in various cell types of the tumor microenvironment. Here, we explored the coagulome of Oral Squamous Cell Carcinoma (OSCC) across tumor types, between OSCC tumors and within individual tumors. The coagulome of OSCC is characterized by a high expression of antipodal activators of coagulation and fibrinolysis, and subpopulations of pro-coagulant and pro-fibrinolytic cancer cells coexist within individual tumors. Importantly, we noted that dendritic cells within OSCC with a procoagulant profile express high levels of key immune checkpoint molecules. Further studies examining a possible negative modulation of the tumor's adaptive immune response by the coagulation process are warranted. Background: Hemostatic complications, ranging from thromboembolism to bleeding, are a significant source of morbidity and mortality in cancer patients. The tumor coagulome represents the multiple genes and proteins that locally contribute to the equilibrium between coagulation and fibrinolysis. We aimed to study the coagulome of Oral Squamous Cell Carcinoma (OSCC) and examine its link to the tumor microenvironment (TME). Methods: We used data from bulk tumor DNA/RNA-seq (The Cancer Genome Atlas), single-cell RNA-seq data and OSCC cells in culture. Results: Among all tumor types, OSCC was identified as the tumor with the highest mRNA expression levels of F3 (Tissue Factor, TF) and PLAU (urokinase type-plasminogen activator, uPA). Great inter- and intra-tumor heterogeneity were observed. Single-cell analyses showed the coexistence of subpopulations of pro-coagulant and pro-fibrinolytic cancer cells within individual tumors. Interestingly, OSCC with high F3 expressed higher levels of the key immune checkpoint molecules CD274/PD-L1, PDCD1LG2/PD-L2 and CD80, especially in tumor dendritic cells. In vitro studies confirmed the particularity of the OSCC coagulome and suggested that thrombin exerts indirect effects on OSCC cells. Conclusions: OSCC presents a specific coagulome. Further studies examining a possible negative modulation of the tumor's adaptive immune response by the coagulation process are warranted.