Myeloid-derived suppressor cell expansion in patients with trans-arterial chemoembolization history

Abstract

Abstract Cancer-specific myelopoiesis causes peripheral myeloid cell expansion and accumulation at the tumor. Myeloid-derived factors negatively regulate anti-tumor immunity. Doxorubicin-eluting bead transarterial chemoembolization (DEB-TACE) can bridge hepatocellular carcinoma (HCC) patients with low stage tumors to liver transplantation (LTx). Unfortunately, HCC recurrence rates remain high, with 5yr tumor-free survival rates estimated at ~50%. Though myeloid-derived suppressor cell (MDSC) expansion has been associated with tumor progression and recurrence risk, the effect of DEB-TACE on MDSC levels is unclear. We observed DEB-TACE HCC patients with disease progression have elevated TGF-β and IL-6 with increased MDSCs at followup. In this study, we prospectively enrolled LTx-candidate HCC patients undergoing DEB-TACE treatment to track MDSCs before and after DEB-TACE treatment based on de novo (DN) verses prior embolization (PE) history. Blood was collected before and < 30 days after DEB-TACE (100–300μm LC Beads™ mixed with 50–75mg doxorubicin). Analyzed were 18 DN patients and 16 PE patients. Tumor diameter and TGF-β levels prior to treatment were similar. CD33+HLA-DRLOW MDSCs were elevated in PE patients both prior to (p<0.05) and following DEB-TACE (p<0.05), but not the number of prior DEB-TACE treatments or radiological treatment response. PE patients with elevated MDSCs (>10%) had elevated TGF-β levels compared to PE patients with <10% MDSCs (p<0.01). PE patients with >10% MDSC also had elevations in IL-6 (p<0.01) and the HCC-recurrence associated MMP-2 (p<0.05). MDSC expansion and elevated TGF-β in HCC patients with DEB-TACE history may identify patients at high risk of early HCC recurrence following LTx.