The Complex Role of Thrombin in Cancer and Metastasis: Focus on Interactions with the Immune System.

Thrombin, a pleiotropic enzyme involved in coagulation, plays a crucial role in both procoagulant and anticoagulant pathways. Thrombin converts fibrinogen into fibrin, initiates platelet activation, and promotes clot formation. Thrombin also activates anticoagulant pathways, indirectly inhibiting factors involved in coagulation. Tissue factor triggers thrombin generation, and the overexpression of thrombin in various cancers suggests that it is involved in tumor growth, angiogenesis, and metastasis. Increased thrombin generation has been observed in cancer patients, especially those with metastases. Thrombin exerts its effects through protease-activated receptors (PARs), particularly PAR-1 and PAR-2, which are involved in cancer progression, angiogenesis, and immunological responses. Thrombin-mediated signaling promotes angiogenesis by activating endothelial cells and platelets, thereby releasing proangiogenic factors. These functions of thrombin are well recognized and have been widely described. However, in recent years, intriguing new findings concerning the association between thrombin activity and cancer development have come to light, which justifies a review of this research. In particular, there is evidence that thrombin-mediated events interact with the immune system, and may regulate its response to tumor growth. It is also worth reevaluating the impact of thrombin on thrombocytes in conjunction with its multifaceted influence on tumor progression. Understanding the role of thrombin/PAR-mediated signaling in cancer and immunological responses is crucial, particularly in the context of developing immunotherapies. In this systematic review, we focus on the impact of the thrombin-related immune system response on cancer progression.

Immunomodulatory Effect of Infectious Disease of a Breastfed Child on the Cellular Composition of Breast Milk.

Recent studies suggest that the content of immune components in milk is influenced by the mother's health and also by the infant she feeds. We aimed to evaluate the effect of a child's respiratory tract infection on the cellular composition of breast milk (neutrophils, monocytes, eosinophils, lymphocytes, and their subpopulations). Twenty-six breastfeeding mothers whose children were hospitalized for respiratory tract infections were enrolled in the study. The control group consisted of 23 mothers of healthy children. Regarding the children, baseline laboratory blood tests were performed, and nasal swabs were taken for the presence of RS virus. In the next step, milk samples were collected from the mothers to assess the cellular composition of the milk, including neutrophils, monocytes, eosinophils, lymphocytes, and their subpopulations. Significantly higher percentages of T lymphocytes (helper and cytotoxic lymphocytes) were observed in the milk of the studied mothers. There was a significantly higher percentage of milk lymphocytes in the group of affected children with confirmed RSV etiology than in children with excluded RSV etiology. A significant positive correlation was observed between the duration of infection and the percentage of milk NK cells and between milk CD19 lymphocytes and the child's serum leukocytosis. This study may provide evidence of a link between cells in breast milk and disease in the breastfed infant. The severity of the infection, its duration, and the etiological agent of the infection may affect the cellular composition of milk.