Role of Intrahepatic Regional Immunity in Post-Transplant Cancer Recurrence

Hepatic malignancy is a major indication for liver transplantation; however, post-transplant cancer recurrence is an emerging clinical challenge affecting long-term outcomes. Pre-transplant tumor biology, staging, and post-transplant immunosuppression regimens have been elucidated as risk factors for recurrent liver cancer. However, increasing evidence indicates that hepatic ischemia and reperfusion (IR) injury to allografts are crucial to providing a favorable immunologic microenvironment for cancer cell invasiveness and metastasis after liver transplantation. The association of severe graft injury in marginal grafts, such as small-for-size or fatty grafts, with lower recurrence-free survival rates in living donor liver transplantations, substantiates the correlation between hepatic IR injury and cancer recurrence. IR has been demonstrated to trigger intrahepatic immunological microenvironment remodeling, including pro-inflammatory responses exacerbating graft injury and anti-inflammatory responses promoting tissue repair. However, the role of regional immunity in post-transplant cancer recurrence is not comprehensively understood. This review describes the up-to-date evidence of the intrahepatic humoral microenvironment and regional regulatory immunological microenvironment induced by IR injury, as well as their roles in cancer recurrence after liver transplantation. A comprehensive understanding of regional immunity will provide novel precise diagnostic, therapeutic, and prognostic strategies for post-transplant cancer recurrence.(c) 2021 THE AUTHORS. Published by Elsevier LTD on behalf of Chinese Academy of Engineering and Higher Education Press Limited Company. This is an open access article under the CC BY-NC-ND license(http://creativecommons.org/licenses/by-nc-nd/4.0/).