Despite significant progresses in the diagnosis and treatment of cancer, it still represents one the leading cause of death in western countries (25% of all deaths), whereas autoimmune diseases still strike millions of people worldwide. The immune system is normally focused on responding to foreign materials. When this process undergoes a wrong regulation, the immune system can attack self-tissues, resulting in autoimmune disease. On the contrary, tumor cells can become invisible to the adaptive immune system, resulting in tolerant or even pro-tumor functions. In cancer, as well as in chronic inflammation and autoimmune diseases, the cellular components of the innate immune system, including dendritic cells, are significant altered in their responses. Oxygen deficiency (tissue hypoxia) is usually present in neoplastic and inflammatory processes. Thus, dendritic cells can be deeply affected by hypoxic stress. In this project, we have found out that hypoxia enhances the expression of a specific extracellular ribonuclease, RNASET2, in human dendritic cells. This molecule is involved in tumor suppression on one hand, and on the other in autoimmune disease. More importantly, it plays several roles mostly related to cellular stress, including exposure to hypoxia. Thus, this project may contribute to a better understanding of the mechanisms involved in the deregulation of the immune system in cancer and autoimmune diseases with important diagnostic and therapeutic implications.