Primary Sclerosing Cholangitis (PSC) is a progressive liver disease for which there is no effective medical therapy. PSC belongs to the family of immune-mediated biliary disorders and it is characterized by persistent biliary inflammation and fibrosis. Here, we explored the possibility of using extracellular vesicles (EVs) derived from human, bone marrow mesenchymal stromal cells (MSCs) to target liver inflammation and reduce fibrosis in a mouse model of PSC. Five-week-old male FVB.129P2-Abcb^4tm1Bor mice were intraperitoneally injected with either 100 µL of EVs (± 9.1 × 10⁹ particles/mL) or PBS, once a week, for three consecutive weeks. One week after the last injection, mice were sacrificed and liver and blood collected for flow cytometry analysis and transaminase quantification. In FVB.129P2-Abcb4^tm1Bor mice, EV administration resulted in reduced serum levels of alkaline phosphatase (ALP), bile acid (BA), and alanine aminotransferase (ALT), as well as in decreased liver fibrosis. Mechanistically, we observed that EVs reduce liver accumulation of both granulocytes and T cells and dampen VCAM-1 expression. Further analysis revealed that the therapeutic effect of EVs is accompanied by the inhibition of NFkB activation in proximity of the portal triad. Our pre-clinical experiments suggest that EVs isolated from MSCs may represent an effective therapeutic strategy to treat patients suffering from PSC.

Prostate cancer (PCa) remains one of the most prevalent and lethal cancers in men, particularly in its metastatic form. Despite therapeutic advancements, resistance to therapy often leads to a castration-resistant state with genetic and molecular alterations that promote immune evasion and disease progression. Chronic inflammation and the immunosuppressive tumor microenvironment (TME) further exacerbate immune dysfunction. The suboptimal clinical success of current immunotherapies in advanced PCa underscores the urgent need to better understand the mechanisms underlying immune escape during disease progression and in response to therapeutic interventions. This review explores the key immune-evasive features of PCa, the contribution of the TME, and the immunotherapeutic strategies that have been clinically evaluated to improve outcomes in patients with advanced disease.