Allogenic Liver Transplantation Inhibits The Growth Of Extrahepatic Tumor In Mice And Its Immunologic Mechanisms

Objectives:Graft versus tumor(GvT)effect,which appears after allogenic hematopoietic stem cell transplantation(alloHSCT),is an anti-tumor effect of various lymphocytes derived from both donors and recipients.Liver is known as an organ that is abundant in both hematopoietic stem cells and various lymphocytes.However,whether allogenic liver transplantation has the similar GvT effect has not been reported.This article aims to verify the GvT effect after allogenic liver transplantation and to explore its immunological mechanisms.Methods:We established a novel animal model of implanting tumor cell lines after allogenic and syngenic orthotopic liver transplantation in mice.By observing and measuring the growth of extrahepatic tumor,we verified the GvT effect of allogenic liver transplantation.Whereafter,we explained the immunological mechanisms of this effect by establishing lymphocyte-depleted donor models and other immunologic experimental technics like immunofluorescence,flow cytometry and in vitro cell co-culture.Results:The animal model of implanting tumor cell lines after orthotopic liver transplantation in mice was successfully established.Tumor growth after allogenic liver transplantation was significantly inhibited and the apoptosis of tumor cells increased.However,these results didn't appear after heart transplantation.At the early period after allogenic liver transplantation,extrahepatic tumor was infiltrated with donor-derived lymphocytes,which was related to GvT effect.When T/B cell-deficient allograft was transplanted,GvT effect no longer existed and tumor-infiltrating lymphocytes decreased.After allogenic liver transplantation,CD69,CD44 and CD25 expression in tumor-infiltrating T cells increased.Finally,stronger cytotoxicity was found in allogenic lymphocytes than syngenic lymphocytes when co-cultured with tumor cells in vitro.Conclusions:GvT effect existed after allogenic liver transplantation as well and was not related to graft rejection.At the early stage after allogenic liver transplantation,extrahepatic tumor was infiltrated with donor-derived lymphocytes that had stronger cytotoxicity than syngenic lymphocytes.In addition,tumor-infiltrating donor-derived lymphocytes could recruit and activate recipient-derived lymphocytes.Both donor-and recipient-derived lymphocytes contributed to the apoptosis of tumor cells and played important roles in GvT effect after allogenic liver transplantation.