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13 March 2020 : Original article  

Recipient Hepatic Tumor-Associated Immunologic Infiltrates Predict Outcomes After Liver Transplantation for Hepatocellular Carcinoma

Georgi Atanasov123ABCDEFG*, Karoline Dino1BCE, Katrin Schierle4CDE, Corinna Dietel1BCE, Gabriela Aust5E, Johann Pratschke2DEG, Daniel Seehofer1E, Moritz Schmelzle12EG, Hans-Michael Hau1ADEF

DOI: 10.12659/AOT.919414

Ann Transplant 2020; 25:e919414


BACKGROUND: Transplantation of the liver entails a state of altered recipient immunologic competence. There are only scarce data concerning the impact of host immunologic factors on the outcome of liver transplant recipients in the context of hepatocellular carcinoma (HCC).

MATERIAL AND METHODS: Our study focused on evaluating the presence of tumor necrosis and frequency levels of angiopoietins and monocytes/macrophages subtypes in the host liver prior to liver transplantation (LTX) and their association with recurrence, graft rejection, survival, and clinical prognosis after LTX. Formation of tumor necrosis and tissue densities of angiopoietins and cellular immunologic infiltrates – CD68⁺ and CD163⁺ macrophages (TAMs) and TIE2-expressing monocytes (TEMs) – were quantified in recipient HCC specimens. The densities were then matched with clinicopathologic variables and patient survival after LTX (n=88). Some patients were treated prior to LTX by neoadjuvant transarterial chemoembolization (TACE, n=55).

RESULTS: Recipient hepatic infiltration with TEMs and CD68⁺ TAMs was associated with decreased 1-, 3-, and 5-year survival, as well as metastatic and recurrent HCC after LTX (all p<0.05). TEMs and infiltrating monocytes/macrophages were associated with angiopoietin expression, metastatic, and recurrent HCC (all p<0.05). Furthermore, hepatic angiopoietin-2 expression was associated with graft rejection after LTX (p<0.05). After TACE and LTX, formation of tumor necrosis was associated with an increased presence of monocytes/macrophages and a reduced incidence of recurrent HCC in the graft (all p<0.05).

CONCLUSIONS: Infiltrating monocytes/macrophages subsets and related angiopoietin axis are associated with worse survival, tumor recurrence, and clinical outcome after LTX for HCC.

Keywords: Angiopoietins, Carcinoma, Hepatocellular, Liver Transplantation, Monocytes, Graft Rejection, Graft Survival, Liver, Liver Neoplasms, Macrophages, tumor microenvironment

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Annals of Transplantation eISSN: 2329-0358
Annals of Transplantation eISSN: 2329-0358