Atanasov Georgi, Dino Karoline, Schierle Katrin, Dietel Corinna, Aust Gabriela, Pratschke Johann, Seehofer Daniel, Schmelzle Moritz, Hau Hans-Michael
Department of Visceral-, Transplantation-, Thoracic- and Vascular Surgery, University Hospital Leipzig, Leipzig, Germany.
Department of Surgery, Campus Charité Mitte und Campus Virchow-Klinikum, Charité - Universitätsmedizin Berlin, Berlin, Germany.
Ann Transplant. 2020 Mar 13;25:e919414. doi: 10.12659/AOT.919414.
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.
背景 肝脏移植会使受体的免疫能力处于改变状态。关于宿主免疫因素在肝细胞癌（HCC）背景下对肝移植受体结局的影响，仅有稀缺的数据。材料与方法 我们的研究聚焦于评估肝移植（LTX）前宿主肝脏中肿瘤坏死的存在情况、血管生成素以及单核细胞/巨噬细胞亚型的频率水平，以及它们与LTX后复发、移植物排斥、生存和临床预后的关联。在受体HCC标本中对肿瘤坏死的形成、血管生成素的组织密度以及细胞免疫浸润——CD68⁺和CD163⁺巨噬细胞（TAM）以及表达TIE2的单核细胞（TEM）进行定量分析。然后将这些密度与临床病理变量以及LTX后的患者生存情况（n = 88）进行匹配。部分患者在LTX前接受了新辅助经动脉化疗栓塞术（TACE，n = 55）。结果 受体肝脏中TEM和CD68⁺ TAM浸润与1年、3年和5年生存率降低以及LTX后HCC转移和复发相关（所有p < 0.05）。TEM以及浸润的单核细胞/巨噬细胞与血管生成素表达、HCC转移和复发相关（所有p < 0.05）。此外，肝血管生成素 - 2表达与LTX后移植物排斥相关（p < 0.05）。TACE和LTX后，肿瘤坏死的形成与单核细胞/巨噬细胞数量增加以及移植物中HCC复发率降低相关（所有p < 0.05）。结论 浸润的单核细胞/巨噬细胞亚群以及相关的血管生成素轴与HCC患者LTX后的较差生存、肿瘤复发和临床结局相关。
