Targeting monoamine oxidase A-regulated TAM polarization for cancer immunotherapy

Abstract

<jats:title>Abstract</jats:title> <jats:p>Targeting tumour-associated macrophages (TAMs) is a promising strategy to modify the immunosuppressive tumour microenvironment and improve cancer immunotherapy. Monoamine oxidase A (MAO-A) is an enzyme best known for its function in the brain; small molecule MAO inhibitors (MAOIs) are clinically used for treating neurological disorders. Here we observed MAO-A induction in mouse and human TAMs. MAO-A-deficient mice exhibited decreased TAM immunosuppressive functions corresponding with enhanced antitumour immunity. MAOI treatment induced TAM reprogramming and suppressed tumour growth in preclinical mouse syngeneic and human xenograft tumour models. Combining MAOI and anti-PD-1 treatments resulted in synergistic tumour suppression. Clinical data correlation studies associated high intratumoural MAOA expression with poor patient survival in a broad range of cancers. We further demonstrated that MAO-A promotes TAM immunosuppressive polarization via upregulating oxidative stress. Together, these data identify MAO-A as a critical regulator of TAMs and support repurposing MAOIs for TAM reprogramming to improve cancer immunotherapy.</jats:p>

Endovascular Occlusion of Giant Posttraumatic Pseudo-Aneurysm of Superior Mesenteric Artery Connected to Mesenteric Arteriovenous Fistula

“…In recent decades, there has been suggested a variety of less traumatic procedures to isolate arteriovenous anastomoses. The list of such surgeries is as follows: a fistula isolation by implanting a drug-eluting stent (graft) in the damaged artery lumen [5,12,13]; fistula occlusion by framing coils [14][15][16][17], adhesive compositions, by Onyx [18]; the occlusion of afferent arteries by nitinol braided occluders -an amplatzer septal occluder, an amplatzer vascular plug, and others [2,11,17,[19][20][21][22][23]. In these cases invasive angiography is used after diagnostic procedures as a navigation technique and to control the effect of an endovascular intervention.…”