Investigation of the role of neoplastic and exosomal arginases in avoiding the anti-neoplastic immune response in ovarian cancer

Ovarian cancer has the highest mortality rate of any cancer of the female reproductive organs, with a 5-year survival rate of only 30% of patients. The reason for such a low survival rate of patients is late diagnosis, caused by the lack of clinical symptoms and the lack of appropriate biomarkers to detect the disease at an early stage. Importantly, while some of the ovarian cancer subtypes initially respond well to therapeutic approaches, subsequent resistance remains a significant clinical problem. Therefore, further research is needed to deepen the understanding of the molecular phenomena occurring in ovarian cancer cells, especially in the context of searching for new therapeutic strategies. As with other cancers, ovarian cancer uses a wide variety of mechanisms to suppress the activity of the immune system. The aim of the project is to comprehensively assess the role of two exosome-related enzymes (arginase 1 and 2) involved in the breakdown of endogenous amino acids in ovarian cancer's ability to escape immune surveillance. The development of chronic inflammation and the induction of enzymatic pathways for arginine breakdown are recognized as important factors involved in this mechanism. Thus, we hypothesize that by releasing arginase-containing exosomes which then spread systemically through the circulatory system, cancer cells lead to a global deficiency of L-arginine and thus to a systemic impairment of T cells necessary for the development of an effective anti-cancer response. Taking into account the recent development of inhibitors of amino acid metabolic pathways, we also assume that inhibition of the enzymatic activity of the above-mentioned enzyme system may be a target for novel anti-cancer strategies, especially in combination with the already existing targeted therapies at the molecular level, but also with classical chemotherapy.