Increased tumor recurrence by M2 macrophages after liver transplantation

Abstract

Objectives Liver transplantation (LT) is a well-established option of cure for hepatocellular carcinoma (HCC) with 5-year survival rates that exceed 70% in Hong Kong. One of the challenges in LT remains to be the high tumor recurrence rate. In the proposed study, we aim to investigate the clinical significances of M2 macrophages in tumor recurrence and the underlying mechanisms after liver transplantation in HCC. Hypothesis to be tested We hypothesize that the ischemia reperfusion injury during transplantation induces the activation of M2 macrophages and subsequently leading to increased tumor recurrence rate and poor survival outcome in HCC patients. Designs and subjects 80 Clinical liver specimens will be collected from HCC patients who underwent either deceased donor (DDLT) or living donor (LDLT) liver transplantation will be collected. A rat liver tumor transplantation model and toll-like receptor 4 knockout mice will be applied to study the M2 macropahges activation and tumor promoting functions in transplantation. Main outcome measures and Data analysis Quantification of M2 macrophages in DDLT and LDLT clinical sample as well as the rat transplant model using quantitative PCR and immunostaining will be performed. The results will be correlated with survival outcomes and tumor recurrence in patients. Expected results The findings provide experimental evidences proving the clinical significances of M2 macrophages in promoting tumor recurrence after liver transplantation. Further in vivo and in vitro studies support the essential roles of TLR4 in M2 activation and protumor activities.